Parkinson's
Episodes
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Rhonda Nutrition Parkinson's Microbiome Omega-3 Sulforaphane Sauna Weight Loss Intestinal Permeability CocoaDr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Rhonda Vitamin D Exercise Brain Alzheimer's Parkinson's Cancer Microbiome Cholesterol Omega-3 Skin Sulforaphane Protein NAD+ Moringa Blood-Brain Barrier CocoaDr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Rhonda Vitamin D Exercise Parkinson's Epigenetics Omega-3 Fasting Melatonin Vaccine Resveratrol Sauna Insulin COVID-19 Cardiovascular AutoimmunityDr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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How epigenetic predictions align with onset of cancer, Parkinson's and Alzheimer's | Steve Horvath ClipA person's epigenetic age correlates with their risk for developing major diseases of aging like cancer, Alzheimer's disease, and Parkinson's.
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In this clip, Dr. Giselle Petzinger describes her recommended components for an exercise program for people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger discusses how no evidence exists that lifestyle factors, such as diet and exercise, can cure Parkinson's disease or obviate the need for dopamine replacement.
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In this clip, Dr. Giselle Petzinger discusses how intense exercise can impact motor scores in people with Parkinson's disease.
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Benefits of 1-on-1 therapy & group dynamics in exercise for Parkinson's patients | Giselle Petzinger ClipIn this clip, Dr. Giselle Petzinger explains how to design an optimal exercise regimen for people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger explains that strenuous exercise affects dopamine sensitivity in the brains of people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger discusses how adding a cognitive load to an exercise program is important for people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger discusses the importance of incorporating intensity into the exercise routine for people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger describes the specific characteristics of exercise that make it so helpful to people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger describes how exercise may provide a repair model that allows some type of resilience against the insults of Parkinson's disease.
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In this clip, Dr. Giselle Petzinger highlights some of the risk factors for Parkinson's disease, and discusses how this is likely a multifaceted problem.
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How loss of dopamine-producing neurons affects brain circuitry and behavior | Giselle Petzinger ClipIn this clip, Dr. Giselle Petzinger explains how the loss of dopamine disrupts circuitry in the brains of people with Parkinson's disease.
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In this clip, Dr. Giselle Petzinger discusses Parkinson's disease and explains how symptoms can vary dramatically between people.
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Dr. Giselle Petzinger discusses new findings in Parkinson's disease research, emphasizing exercise's role in delaying disease progression.
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Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Increasing general autophagy as a treatment for neurodegenerative diseases like Parkinson's disease ClipDr. Guido Kroemer describes how mitophagy contributes to the pathophysiology of neurodegenerative disease and how autophagy might mitigate these processes.
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Dr. Gordon Lithgow discusses the roles of protein aggregation, iron overload, and others in the aging process.
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Dr. George Brooks discusses the metabolic pathway known as the “lactate shuttle" and its role in the recovery from traumatic brain injury.
Topic Pages
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Autophagy
Parkinson’s pathology involves impaired PINK1-Parkin–dependent mitophagy, blocking autophagic clearance of damaged mitochondria and α-synuclein aggregates.
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Berberine
Preclinical data indicate berberine mitigates Parkinson's dopaminergic neurodegeneration via AMPK/Nrf2 activation and α-synuclein aggregation suppression.
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Brain-derived neurotrophic factor (BDNF)
Nigral BDNF deficiency diminishes TrkB signaling, weakening dopaminergic neuron survival and accelerating Parkinsonian neurodegeneration.
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Melatonin
Melatonin’s MT1/MT2 receptor signaling and antioxidant actions mitigate dopaminergic oxidative stress and α-synuclein aggregation in Parkinson’s models.
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Small vessel disease
No proven mechanistic link exists; cerebral small vessel disease causes arteriolosclerotic lumen narrowing, chronic hypoperfusion, white-matter infarction.
News & Publications
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Different exercise training intensities have varied effects on symptoms of Parkinson's disease. journals.physiology.org
Parkinson’s disease affects more than 10 million people worldwide. Evidence suggests that exercise markedly improves the quality of life for those with the condition. A recent study found that different exercise training intensities have varied effects on symptoms of Parkinson’s disease.
Researchers randomly assigned 29 people with Parkinson’s disease to either 10 weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). They measured the participants' change in maximal oxygen consumption (VO2peak, a measure of cardiorespiratory fitness) and changes in their motor symptoms, fatigue, cardiovascular measures, gait, balance, strength, and endurance.
They found that exercise training increased the participants' VO2peak, especially among those in the HIIT group. Participants' motor symptoms improved over time, but with little difference between the two groups. Both groups reported less fatigue, but their gait, balance, blood pressure, and heart rate did not change. Participants' strength increased similarly in both groups, but only the HIIT group showed increased muscular endurance.
These findings suggest that high-intensity interval training and moderate-intensity continuous training effectively improve cardiorespiratory fitness and reduce motor symptoms and fatigue in people with Parkinson’s. However, HIIT may provide additional benefits, such as greater improvements in VO2peak and increased muscular endurance. Learn more about exercise as a treatment for Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Drinking caffeinated coffee reduces the risk of Parkinson's disease by 37 percent. www.neurology.org
Coffee is perhaps best known for its stimulant properties, primarily from its caffeine content. Recent research found that caffeine and its metabolites reduce the risk of Parkinson’s disease, a progressive neurodegenerative disorder affecting more than 10 million people worldwide.
The research was part of the EPIC study, a large, prospective cohort that spans six European countries. Researchers looked at how much coffee participants reported drinking and then tracked who developed Parkinson’s. They used statistical models to estimate the risk of developing the disease and analyzed caffeine metabolites in blood samples taken several years before any Parkinson’s diagnosis.
They found that participants who drank the most coffee had a 37 percent lower risk of developing Parkinson’s than non-coffee drinkers. In addition, higher levels of caffeine and its principal metabolites (paraxanthine and theophylline) were associated with a lower risk of Parkinson’s, even after considering other risk factors, such as smoking and alcohol use.
These findings suggest that drinking caffeinated coffee protects against Parkinson’s disease. However, coffee is also rich in other bioactive compounds, including polyphenols, alkaloids, and others – many of which exert potent neuroprotective effects.
While some forms of Parkinson’s disease are genetic, most cases involve a complex interaction between genetic and environmental risk factors. Learn more in this clip featuring Dr. Giselle Petzinger.
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Polyphenols in tea may reduce symptoms and progression of Parkinson's disease. pubmed.ncbi.nlm.nih.gov
Parkinson’s disease is a progressive neurodegenerative disorder characterized by loss of dopamine-producing neurons, motor impairments, and the accumulation of alpha-synuclein, a neuronal protein that regulates synaptic vesicle movements and neurotransmitter release. However, a growing body of evidence suggests that dietary components protect against the development and progression of the condition. A 2015 study found that polyphenols in tea mitigated neuronal loss, motor impairments, and alpha-synuclein accumulation in a primate model of Parkinson’s disease.
Researchers treated a group of monkeys with Parkinson’s disease with a mixture of tea polyphenols, including epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate (commonly known as EGCG), daily for 80 days. Another group of monkeys received no treatment. The researchers assessed the animals' motor function every two weeks and examined their brains.
They found that treatment with tea polyphenols alleviated motor impairments and neuronal loss in the monkeys and reduced alpha-synuclein accumulation. Monkeys that didn’t receive polyphenols showed marked disease progression.
These findings suggest that tea polyphenols exert neuroprotective properties in a primate model of Parkinson’s disease. Polyphenols are one of the most common classes of bioactive compounds found in plants. Evidence suggests they exert potent anti-inflammatory, antioxidant, and cardioprotective properties. Learn more about polyphenols in our overview article.
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High particulate matter exposure increases the risk of Parkinson's disease by nearly 20 percent. www.neurology.org
People who live in large cities or near industrial areas are often exposed to high levels of particulate matter – a mixture of solid particles and liquid droplets in air pollution that forms fine inhalable particles with diameters typically 2.5 micrograms (PM2.5) or less. A recent study found that high exposure to PM2.5 increases the risk of developing Parkinson’s disease by nearly 20 percent.
Researchers conducted a population-based study of more than 21 million older adults living in the US. They assessed their exposure to particulate matter based on their geographical location and ascertained whether they had Parkinson’s disease based on Medicare records.
They found that people exposed to the median PM2.5 level were 56 percent more likely to develop Parkinson’s than those with the lowest PM2.5 exposures. For every additional microgram per cubic meter of PM2.5 exposure, risk increased by 4.2 percent. In the Mississippi-Ohio River Valley, where particulate matter levels are high, the risk of developing Parkinson’s disease was 19 percent greater than in the rest of the country.
These findings suggest that exposure to particulate matter markedly increases a person’s risk of developing Parkinson’s disease, aligning with other evidence pointing to the disease’s environmental origins. Parkinson’s disease is a neurodegenerative disorder that affects the central nervous system. Caused by the destruction of nerve cells in the part of the brain called the substantia nigra, it typically manifests later in life and is characterized by tremors and a shuffling gait. Learn more about Parkinson’s disease and therapies in this episode featuring Dr. Giselle Petzinger.
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Herbicide exposure linked to impaired neurobehavioral performance in teens. neurosciencenews.com
Exposure to environmental toxins can harm brain health, especially in teens and children, who are fundamentally more vulnerable than adults to toxic exposures. Herbicides to control weeds and insect repellents to control vector-borne diseases are prevalent worldwide, but scientists don’t fully understand their effects on brain health. A new study shows that exposure to common herbicides impairs teen neurobehavioral performance.
Researchers measured urinary concentrations of common herbicides (glyphosate and 2,4-D) and an insect repellent (N,N-diethyl-meta-toluamide, commonly known as DEET) in 519 teens living in agricultural communities in Ecuador. They tested the teens' neurobehavioral performance in five areas: attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception.
They detected glyphosate in the urine of 98.3 percent of the teens and 2,4-D in 66.2 percent. Higher glyphosate concentrations correlated with lower scores in social perception; higher 2,4-D concentrations correlated with lower scores in attention/inhibitory control, memory/learning, and language. DEET exposure did not influence neurobehavioral performance.
Glyphosate is a broad-spectrum herbicide widely used in agriculture and forestry to control unwanted vegetation. It is known for effectively eliminating weeds and has been a key component of many commercial herbicide products, including Roundup. However, the use of glyphosate has also been a subject of controversy due to concerns about its potential harm to human health and the environment.
These findings suggest that herbicide exposure negatively influences neurobehavioral performance in teens. Listen to Dr. Rhonda Patrick discuss herbicides, pesticides, and disease risk in this Q&A.
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Playing American football linked to a 61 percent higher risk of parkinsonism and Parkinson's disease. neurosciencenews.com
The relationship between repetitive blows to the head (as in boxing) and parkinsonism and Parkinson’s disease is well established. However, scientists don’t fully understand the relationship between American football and these conditions. A recent study found that playing American football increases a person’s risk of parkinsonism and Parkinson’s disease by 61 percent.
Researchers conducted a cross-sectional study using data from 1,875 men enrolled in the Fox Insight study, in which participants completed online questionnaires regarding their health status. They collected data on aspects of football participation, including duration of play, highest level played, and age at first exposure. The analysis accounted for various factors, including age, education, medical history, body mass index, concussions, and family history of Parkinson’s disease.
They found that those who had played football were 61 percent more likely to report having parkinsonism or Parkinson’s disease than those who did not. Those who experienced higher levels of play (such as college or professional level) were nearly three times more likely to report being diagnosed with these conditions.
Parkinsonism is an umbrella term that describes a group of neurological disorders that share similar symptoms with Parkinson’s disease, including tremors, muscle stiffness, slow movement, and difficulties with balance and coordination. Parkinson’s disease is the primary cause of parkinsonism, driving approximately 80 percent of all cases.
These findings suggest that playing American football markedly increases the risk of parkinsonism and Parkinson’s disease. However, this study does not prove causation but highlights a potential link between sports-related head injuries and long-term neurological consequences. Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Presence hallucinations, such as sensing an unseen person, in early Parkinson's may signal faster cognitive decline. www.medicalnewstoday.com
Cognitive decline and hallucinations are common features of late-stage Parkinson’s disease. However, during the early stages of the disease, many people experience minor hallucinations – such as sensing an unseen person nearby or seeing a shadow pass in one’s peripheral vision – potentially indicating future cognitive deline. A recent study found that people with Parkinson’s disease who experienced minor hallucinations exhibited altered brain wave activity.
Researchers interviewed 75 people with Parkinson’s disease to determine whether they experienced minor hallucinations. Then, using electroencephalography (EEG), they analyzed their brain wave activity. They repeated the EEG five years later.
They found that those who experienced minor hallucinations – roughly half of the participants – had altered theta oscillations in the frontal part of their brains. These alterations were associated with poorer cognitive abilities in the frontal and subcortical regions of the brain. At the five-year follow-up, they found that participants with more frontal theta alterations during the initial assessment had a greater decline in their frontal and subcortical cognitive functions.
Theta oscillations are rhythmic, electrical brain waves occurring at approximately four to eight cycles per second, typically observed during deep relaxation, daydreaming, and certain stages of sleep. Theta waves play a crucial role in various cognitive processes, such as memory formation, learning, and spatial navigation. They enable communication and synchronization between brain regions, facilitating efficient information processing and integration.
These findings suggest that changes in frontal theta oscillations could be an early marker for cognitive decline in people with Parkinson’s disease. Exercise may slow the progression of Parkinson’s disease. Learn more in this episode featuring Parkinson’s expert Dr. Giselle Petzinger.
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Artificial intelligence tool shows 96 percent accuracy in early Parkinson's disease diagnosis. parkinsonsnewstoday.com
Early diagnosis of Parkinson’s disease is important because many commonly used treatments for the condition are more effective when administered early on. New research suggests that a new artificial intelligence tool can help diagnose Parkinson’s disease well before symptoms manifest, with 96 percent accuracy.
Researchers used machine learning to analyze metabolites – byproducts of metabolism – in the blood of 78 people, half of whom had Parkinson’s disease.
They found that the machine learning tool was approximately 96 percent accurate when differentiating between healthy people and those with Parkinson’s disease, based on their blood metabolites. They also found that people with Parkinson’s disease were more likely to have high levels of a poly-fluoroalkyl substance in their blood and low levels of triterpenoids, cholestane steroids, and diacylglycerol.
Polyfluoroalkyl substances, also known as PFAS, are man-made chemicals used in food packaging, household products, and drinking water. PFAS are not excreted in bodily fluids like sweat or urine; rather, they persist in the body for indefinite periods and are often referred to as “forever chemicals.” Triterpenoids, cholestane, and diacylglycerol are plant-based bioactive dietary compounds that exert antioxidant and neuroprotective effects.
These findings suggest that machine learning is a useful tool in detecting Parkinson’s disease early based on metabolites in blood. They also highlight possible interventions to reduce the risk of developing the disease, such as reducing exposure to PFAS and including plant-based bioactive compounds in the diet. Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Physical activity may protect women against Parkinson's disease. www.medscape.com
Parkinson’s disease is a neurodegenerative disorder that affects the central nervous system. New research suggests that exercise reduces the risk of developing Parkinson’s disease. Women who regularly engaged in physical activity were 25 percent less likely to develop the disease than inactive women.
Researchers gathered information about the lifestyles and medical histories of more than 99,000 women and categorized them according to their activity levels. Then, using a statistical method that accounted for the reduced activity that might precede a diagnosis of Parkinson’s disease, they investigated the effects of exercise on Parkinson’s disease risk.
They found that physical activity levels were consistently lower in women who developed Parkinson’s disease than in those who did not, even up to 29 years before the disease was diagnosed. The difference between the two groups became more pronounced around 10 years before diagnosis. Overall, women with the highest activity levels had a 25 percent lower risk of developing Parkinson’s disease than those with the least activity, even after considering other risk factors.
These findings suggest that exercise protects women against Parkinson’s disease. The mechanisms that drive this protective effect may be related to exercise’s capacity to regulate key neurotransmitters, promote the release of brain-derived neurotrophic factor (BDNF), ameliorate brain inflammation, and reduce oxidative stress. Interestingly, exercise also benefits people after they have been diagnosed with Parkinson’s disease. Learn more in this clip featuring Dr. Giselle Petzinger.
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Gut bacteria implicated in Parkinson's disease pathophysiology. medicalxpress.com
Aggregates of alpha-synuclein – a protein present in the human brain – are a hallmark of Parkinson’s disease. But what triggers the protein’s aggregation has long remained a mystery. New research suggests that bacteria in the gut drive alpha-synuclein aggregation, contributing to the pathophysiology of Parkinson’s disease.
Researchers isolated a type of bacteria called Desulfovibrio from fecal samples taken from 10 people with Parkinson’s disease and their healthy spouses. Then they fed the bacteria to a type of worm often used to study Parkinson’s disease.
They found that worms fed Desulfovibrio bacteria from people with Parkinson’s disease had more and larger alpha-synuclein aggregates than those fed Desulfovibrio bacteria from healthy people. The Desulfovibrio-fed worms were also more likely to die prematurely.
These findings suggest that Desulfovibrio bacteria contribute to the pathophysiology of Parkinson’s disease. Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Aerobic exercise improves symptoms of Parkinson’s disease, a comprehensive analysis of several studies has found. The beneficial effects of exercise lasted up to six months post-intervention.
Researchers analyzed the findings of 20 studies involving 450 people with Parkinson’s disease. The studies, which lasted between three weeks and six months, employed a variety of aerobic exercise interventions, such as treadmill training, walking, cycling, dancing, and others.
They found that participants who engaged in regular aerobic exercise performed better on tests of mobility, balance, stride/step length, gait velocity, and motor function than those who did not. One of the studies found that the effects on motor function endured up to six months after the intervention ended. Two of the studies showed that exercise also improved the participants' quality of life.
Parkinson’s disease is a neurodegenerative disorder that is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. It typically manifests later in life and is characterized by tremors, poor balance, and a shuffling gait.
These findings support the use of exercise as a means to improve many of the symptoms of Parkinson’s disease. Learn more about the importance of exercise in managing Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Castration-induced sudden drop in testosterone caused Parkinson's symptoms in mice. (2013) www.sciencedaily.com
From the article:
“While scientists use different toxins and a number of complex genetic approaches to model Parkinson’s disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice,” said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush. “We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson’s pathology in male mice.”
“In men, testosterone levels are intimately coupled to many disease processes,” said Pahan. Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year. However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson’s disease.
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“This study has become more fascinating than we thought,” said Pahan. “After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production.”
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Testosterone may cause sex differences in Parkinson's disease risk, rodent study suggests. (2015) www.sciencedaily.com
From the article:
Parkinson’s is due to the loss of dopamine neurons, cells in the region of the brain that controls movement. Oxidative stress, which is a chemical imbalance triggered by sources such as genetic mutations and exposure to environmental toxins, can harm and kill cells. Researchers at the University of North Texas Health Science Center observed in rats' dopamine neurons that testosterone exacerbated damage induced by oxidative stress, acting through a protein called cyclooxygenase 2 (COX2). Blocking the actions of COX2 blocked testosterone’s effects. These data indicate that testosterone may enhance the damage and death in dopamine neurons induced by oxidative stress, explaining the sex differences in the occurrence of Parkinson’s, the researchers wrote
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Selective inhibition of soluble TNF prevented neuron loss and reduced motor deficits in a rat model of Parkinson's disease. (2014) www.sciencedaily.com
From the article:
Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs used to treat disorders such as rheumatoid arthritis.
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Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson’s disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson’s disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.
When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. That compares to controls in which 55 percent of the same neurons were lost. By reducing dopamine neuron loss with XPro1595, the researchers were also able to reduce motor impairment. In fact, the degree of dopamine cell loss was highly correlated both with the degree of motor impairment and immune cell activation.
When XPro1595 is given two weeks after injection, 44 percent of the vulnerable neurons are still lost, suggesting that there is a limited window of opportunity to intervene.
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Estrogen improves symptoms in a mouse model of Parkinson's disease. (2019) www.sciencedaily.com
From the article
Estrogen is thought to protect movement neurons from Parkinson’s disease, but how is unknown. Since the patients more susceptible to Parkinson’s disease – men and post-menopausal women – have low estrogen levels, estrogen treatment might be an effective way to delay and reduce symptoms.
Silke Nuber and colleagues at Harvard Medical School treated mouse models of Parkinson’s disease with brain-selective estrogen and compared the motor performance of males and females before and after treatment. The female mice showed less severe symptoms at a later age, but estrogen still improved their symptoms. In male mice, the estrogen treatment reduced alpha-synuclein breakdown and buildup and helped with severe symptoms, suggesting that estrogen could be a viable treatment option for Parkinson’s patients with low estrogen levels.
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Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in rat models of Parkinson's disease. (2006) TNF-alpha plays a central role in nerve and brain self-repair in a mouse model of demyelination. (2001)
From the article:
In addition to its beneficial role, TNF has been a suspected player in Parkinson’s because elevated levels of it are found in post-mortem brains and cerebrospinal fluid of people with the disease. A previous study by other researchers found that non-steroidal anti-inflammatory drugs that block production of TNF and related molecules can reduce the risk of developing Parkinson’s by 46 percent.
In the current study, UT Southwestern researchers injected two different substances into the rats' brains to cause cell death in the substantia nigra —low-dose infusion of LPS, a toxin from bacteria often used to mimic chronic inflammation of the central nervous system, and 6-hydroxydopamine, which kills cells by creating an overwhelming amount of reactive oxygen and nitrogen molecules. Cell death was measured by counting neurons in stained brain slices.
When an experimental TNF inhibitor called XENP345, designed specifically to block soluble TNF, was also introduced into the brain, dopamine neuron death was reduced by about half.
The same effect was found on cultured dopamine neurons exposed to either toxin.
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Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in models of Parkinson’s disease. (2006) www.sciencedaily.com
Blocking the action of TNF-alpha may slow the progression of Parkinson’s disease.
Parkinson’s disease is a progressive neurodegenerative disorder that affects the central nervous system. It is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. Approximately 1 percent of all adults over the age of 60 years lives with Parkinson’s disease. Findings from a 2006 study suggest that blocking the action of tumor necrosis factor-alpha slows the progression of Parkinson’s disease.
Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders, including cancer, autoimmune diseases, Alzheimer’s disease, and depression.
The investigators injected the brains of mice with either lipopolysaccharide (LPS, an endotoxin that promotes acute inflammation) or 6-hydroxydopamine (a neurotoxin) and assessed the animals' brains for evidence of substantia nigra cell death. They injected a compound called XENP345 (a TNF-alpha inhibitor) into the brains of some of the mice. They also applied LPS and 6-hydroxydopamine to cultured neuronal cells and assessed the effects of XENP345 on cell death.
They found that both LPS and 6-hydroxydopamine caused marked cell death in the substantia nigra region of the animals' brains. They also found that inhibiting TNF-alpha via XENP345 in the brains and in cultured cells reduced cell death by roughly half.
These findings suggest that inhibiting the activity of the pro-inflammatory cytokine TNF-alpha reduces cell death in an animal model of Parkinson’s disease. Robust evidence indicates that exercise, which also reduces inflammation, slows the progression of Parkinson’s disease. Learn more about the effects of exercise on Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.
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Glutathione depletion as a mechanism of Parkinson's disease: midlife depletion in animals induces symptoms and disability www.sciencedaily.com
Depleting glutathione may cause Parkinson’s:
Mice induced to have glutathione depletion as young adults did not develop Parkinsonian-like nerve damage and symptoms, while those who suffered from the depletion in late middle age did develop a loss of dopaminergic neurons specifically related to PD.
Tthe study suggests that loss of glutathione in the affected neurons may impact on energy production in the mitochondria, the “power plant” of the cells. This appears to involve a particular enzyme complex called mitochondrial complex I. Enzymatic activity of this complex has been found to be compromised in PD patients, but to date it has not been clear how this inhibition occurs.
Ameliorating with intravenous glutathione:
A pilot study in 1996 in which a small group of untreated PD patients were given daily intravenous infusions of glutathione over the period of a month reportedly resulted in a significant improvement in disability.“
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Sulforaphane from broccoli sprouts increase glutathione in the brain by an average of 30% with a 100 micromole per day dose www.sciencedaily.com
Increases of glutathione reverse pattern of brain cell activity associated with schizophrenia:
They used the chemical sulforaphane found in broccoli sprouts, which is known to turn on a gene that makes more of the enzyme that sticks glutamate with another molecule to make glutathione. When they treated rat brain cells with glutathione, it slowed the speed at which the nerve cells fired, meaning they were sending fewer messages. The researchers say this pushed the brain cells to behave less like the pattern found in brains with schizophrenia.
However, the impact of sulforaphane may be broader due to the broader effect of increasing glutathione, including in the hippocampus (region impacted by Alzheimer’s disease):
For their study, published in April 2018 in Molecular Neuropsychiatry, the researchers recruited nine healthy volunteers (four women, five men) to take two capsules with 100 micromoles [17.729mg] daily of sulforaphane in the form of broccoli sprout extract for seven days.
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The researchers used MRS again to monitor three brain regions for glutathione levels in the healthy volunteers before and after taking sulforaphane. They found that after seven days, there was about a 30% increase in average glutathione levels in the subjects' brains. For example, in the hippocampus, glutathione levels rose an average of 0.27 millimolar from a baseline of 1.1 millimolar after seven days of taking sulforaphane.
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Inherited Parkinson's LRRK2 mutations promote excessive inflammatory cytokines that cross blood-brain barrier, trigger neuron damage via microglia www.sciencedaily.com
From the article:
Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent – the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.
When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.
Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.
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Repurposed chemo drug acting on the blood-brain barrier shows dose-dependent increase of dopamine in Parkinson's disease patients www.sciencedaily.com
Repurposed chemo drug inactivates protein that destroy’s the blood-brain barrier in Parkinson’s disease:
The current part of the study just published, examined the cerebrospinal fluid of patients via epigenomics, which is a systematic analysis of the global state of gene expression, in correlation with continuing clinical outcomes. The new analysis helps explain the clinical findings.
Nilotinib inactivated a protein (DDR1) that was destroying the ability of the blood brain barrier to function properly. When DDR1 was inhibited, normal transport of molecules in and out of the brain filter resumed, and inflammation declined to the point that dopamine, the neurotransmitter depleted by the disease process, was being produced again.
After 27 months, nilotinib was found to be safe, and patients who received nilotinib showed a dose-dependent increase of dopamine, the chemical lost as a result of neuronal destruction.
First study to show blood-brain barrier as therapeutic target for Parkinson’s disease:
“Not only does nilotinib flip on the brain’s garbage disposal system to eliminate bad toxic proteins, but it appears to also repair the blood brain barrier to allow this toxic waste to leave the brain and to allow nutrients in,” Moussa explains. “Parkinson’s disease is generally believed to involve mitochondrial or energy deficits that can be caused by environmental toxins or by toxic protein accumulation; it has never been identified as a vascular disease.”
“To our knowledge, this is the first study to show that the body’s blood brain barrier potentially offers a target for the treatment for Parkinson’s disease,” Moussa says.
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Environmental toxins inhaled through nose may induce inflammation which culminates in the deposit of Lewy bodies in the brain, promoting Parkinson's www.sciencedaily.com
Lewy bodies found in olfactory areas suggest not only is lost smell a sign of neural damage, but rather a direct link to the mechanism creating the disorder:
The loss of a sense of smell is known to be one of the earliest signs of Parkinson’s disease (PD) and can even appear years before the characteristic tremors and loss of motor function are seen. Some scientists believe that olfactory dysfunction may not just be a sign of broader neural damage, but rather may have a more direct linkage to the generation of the disorder itself. In support of this idea, deposits of a protein called alpha-synuclein that form Lewy bodies can be found in olfactory areas, as well as in dying dopamine neurons whose loss triggers PD, and mutations in the gene encoding alpha-synuclein produce PD.
Inflammation triggered in the areas where the olfactory neurons project (recapitulated by lipopolysaccharide) culminate in alpha-synuclein that can cross the blood-brain barrier:
Results of the study, published in the journal Brain Pathology, showed that application of an irritating component of a bacterium’s cell wall induces inflammation in the areas exactly where the olfactory neurons project, called the olfactory bulb. Moreover, these areas show the hallmark signs of PD, depositions of alpha-synuclein, the core components of Lewy bodies. PD is characterized by progressive motor and non-motor symptoms linked to alpha-synuclein pathology and the loss of dopaminergic neurons in the nigrostriatal system. Toxic aggregates of alpha-synuclein can arise from either overexpression of the protein, changes in protein modifications, and from hereditary mutations.
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“Data from our study show that the bacterial trigger does not move across the blood-brain barrier,” said Quan. “Rather, a sequential inflammatory activation of the olfactory mucosa triggers a subsequent expression of inflammatory molecules within the brain, propagating the inflammation.”
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D-beta-hydroxybutyrate supplementation restored impaired brain function and protected against neurodegeneration in mouse model of Parkinson's disease www.sciencedaily.com
From the article:
Infusion of D-beta-hydroxybutyrate (D-beta-HB) to mice suffering from Parkinson disease restored impaired brain function and protected against neurodegeneration and motor skill abnormalities.
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Przedborski and colleagues administered the neurotoxin MPTP to mice, which caused dopaminergic neurodegeneration and deficits in the mitochondrial electron transport chain reminiscent of Parkinson disease. Using this model of disease, the authors showed that the infusion of the ketone body D-beta-HB restored mitochondrial respiration and protected against MPTP-induced neurodegeneration and motor deficits. The study supports a critical role for mitochondrial defect in Parkinson disease.
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SARS-CoV-2 protein drives alpha synuclein aggregation, a hallmark of Parkinson's disease. medicalxpress.com
Scientists have identified an emerging pattern of associations between SARS-CoV-2 (the virus that causes COVID-19) and Parkinson’s disease. For example, the loss of smell is one of the most common symptoms reported in SARS-CoV-2 infection, but it is also an early symptom of Parkinson’s disease, often preceding diagnosis by many years. In addition, some recent case reports describe patients who presented with probable Parkinson’s disease after recovering from severe SARS-CoV-2 infection. Now, evidence from a recent study suggests that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein, a hallmark of Parkinson’s disease.
SARS-CoV-2 nucleocapsid proteins are helical structures that are housed within the viral membrane. They encapsulate SARS-CoV-2’s genome, protecting it from the host cellular environment. The virus produces large quantities of nucleocapsid proteins once inside an infected cell because they play critical roles in virion assembly and viral replication.
Alpha synuclein is a type of neuronal protein that regulates synaptic vesicle movements and neurotransmitter release. Its aggregation, a progressive process that spreads from cell to cell, impairing brain function, is a dominant feature in the pathophysiology of Parkinson’s disease.
The authors of the report assessed alpha synuclein aggregation in both the absence and presence of the SARS-CoV-2 spike protein (the virus’s primary infectious particle) and the nucleocapsid protein. They found that in the absence of any SARS-CoV-2 proteins, aggregation naturally occurred after about 10 days. The spike protein had no effect on aggregation time, but following exposure to the nucleocapsid protein, aggregation occurred in less than one day – more than 10 times faster than normal.
Then they studied the effects of the nucleocapsid protein in a cell model of Parkinson’s disease. They injected some of the cells with nucleocapsid protein (about the amount one would expect during SARS-CoV-2 infection) and alpha synuclein and injected some with alpha synuclein alone. They found that twice as many cells injected with both proteins died compared to those injected with alpha synuclein alone.
These findings suggest that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein and promotes cells death in a model of Parkinson’s disease. Learn more about Parkinson’s disease in this episode featuring Dr. Gizelle Petzinger.
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Influenza infection may increase a person's risk for Parkinson's disease. www.the-scientist.com
Parkinson’s disease, a neurodegenerative disorder that affects the central nervous system, is caused by destruction of nerve cells in the part of the brain called the substantia nigra. Symptoms of Parkinson’s disease typically manifest later in life and are characterized by tremors and a shuffling gait. Findings from a new study indicate that influenza infection may increase a person’s risk for Parkinson’s disease.
Bacterial and viral infections typically resolve quickly, but in some cases, they elicit long-term adverse effects on human health. For example, streptococcus bacterial infection, which causes strep throat, increases a person’s risk for rheumatic fever, causing fatigue, joint pain, and a dangerous buildup of fluid around the heart. Similarly, human papilloma virus infection, a generally mild sexually transmitted disease, can increase a person’s risk for certain types of cancer. And a growing body of evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, is associated with long-term complications that last several weeks or months, a phenomenon previously referred to as “long COVID” and now known as “Post-Acute Sequelae after SARS-CoV-2 infection.”
The authors of the current study drew on data from the Danish National Patient Registry, a longitudinal registration of detailed administrative and clinical data used exclusively for research. They analyzed more than 61,000 patient records spanning nearly 40 years (1977 to 2016) to identify people who had been diagnosed with influenza and/or Parkinson’s disease.
They found that more than 10,000 people had been diagnosed with Parkinson’s disease during the study period. Those who were diagnosed with influenza (but not other viral infections) were 73 percent more likely to be diagnosed with Parkinson’s more than ten years later, compared to people who had never had an influenza diagnosis. When the researchers restricted the time frame of when the people were diagnosed with influenza to the peak influenza season (when it was less likely to be a false-positive diagnosis), the association with Parkinson’s disease was even stronger.
These findings suggest that influenza infection increases the risk of developing Parkinson’s disease. The authors of the study posited that the mechanisms that drive this association may be related to inflammatory responses during a viral infection that could promote subsequent neurodegeneration, but they caution that their findings were observational and therefore not causal.
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Parkinson’s disease is a progressive neurodegenerative disorder that affects more than 10 million people worldwide. The neuropathological hallmarks of Parkinson’s disease are the loss of dopamine-producing neurons in the substantia nigra region of the brain and the aggregation of alpha synuclein, a type of protein. People who have Parkinson’s disease experience both motor symptoms (such as tremors and a shuffling gait) and non-motor symptoms (such as pain, fatigue, and difficulty concentrating or remembering). Findings from a new study suggest that people with Parkinson’s disease have defects that promote poor blood-brain barrier function, impairing angiogenesis and autophagy.
The blood-brain barrier is a lining of epithelial (skin-like) cells that exchanges nutrients, waste, and signaling molecules. The integrity of the blood-brain barrier relies on angiogenesis,the process by which new blood vessels form in response to various cell signaling molecules and growth factors. Autophagy also supports epithelial health by sequestering protein aggregates, pathogens, and damaged or dysfunctional organelles so they can be broken down and re-used. It performs both a general housekeeping role and a targeted cleansing strategy to maintain cellular health. Autophagy is impaired in Parkinson’s disease, reducing clearance of alpha synuclein aggregates and driving neuronal death.
The investigators previously found that nilotinib, a drug commonly used to treat chronic myelogenous leukemia, halted some of the motor and non-motor symptoms of Parkinson’s disease. The current study clarified the mechanisms that drove these improvements by analyzing cerebrospinal microRNAs, small, non-coding RNA molecules that play important roles in regulating gene expression. Previous research has identified abnormal levels of microRNAs that control genes associated with autophagy in the cerebrospinal fluid of people with Parkinson’s disease. These microRNAs drive the upregulation of proteins that promote degradation of the blood-brain barrier.
The investigators randomly assigned 75 people with Parkinson’s disease to receive 150 or 300 milligrams of nilotinib or a placebo every day for a year. They collected cerebrospinal fluid samples from the participants at the end of the year and conducted genetic sequencing of RNA that they had isolated in the fluid.
They found that after participants were on nilotinib for one year, their cerebrospinal fluid levels of microRNAs that control genes and pathways involved in angiogenesis, autophagy, and collagen (a component of the blood-brain-barrier) increased, and their symptoms improved. Participants who received the placebo did not experience these changes and improvements.
These findings demonstrate that people with Parkinson’s disease have altered expression of genes involved in blood-brain-barrier integrity and autophagy. They further indicate that addressing vascular defects associated with Parkinson’s disease may be beneficial in treating some of the symptoms that accompany the disorder.
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Dancing slows the progression of Parkinson's disease symptoms. www.eurekalert.org
Parkinson’s disease is a progressive, incurable neurodegenerative disorder that typically manifests later in life. It is characterized by motor features, such as tremors and a shuffling gait, but can include non-motor features as well, such as fatigue, sleep problems, and mood disorders. Findings from a new study suggest that dancing can slow the progression of both motor and non-motor symptoms of Parkinson’s disease.
A growing body of evidence indicates that physical activities that incorporate learning or skill development are particularly beneficial for people with Parkinson’s disease. Skill-based exercises, such as tennis, yoga, and non-contact boxing, involve goal-oriented movement in which accuracy is important to accomplish the desired outcome. Elements of practice, repetition, feedback, and learning are features of exercise that may be beneficial for people with Parkinson’s disease.
The study involved 16 adults (average age, 69 years) with mild severity Parkinson’s disease. Participants attended a 75-minute structured, supervised dance class once a week for three years. The dancing including both high- and low-intensity activities. Age- and disease severity-matched adults who did not participate in the dance intervention served as a reference group. The authors of the study assessed the participants' motor and non-motor symptoms (and how those symptoms affected aspects of daily living) at various timepoints during the intervention, based on the Unified Parkinson’s Disease Rating Scale (UPDRS), a widely accepted assessment of disease severity.
The assessments revealed that participants who engaged in the dance intervention experienced no motor impairment over the three-year study period. Those who did not dance (the reference group) showed normal motor declines during that time. Participants who danced also experienced no declines motor aspects of daily living (such as those related to speech and balance) or in non-motor aspects of daily living (such as cognitive function and mood).
These findings suggest that skill-based dancing slows the progression of motor and non-motor symptoms associated with Parkinson’s disease. This was a small study, however, so more research is needed to confirm these findings. Learn more about the benefits of skill-based exercise for people with Parkinson’s disease in this clip featuring Dr. Giselle Petzinger.
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Compound found in sesame seeds may protect against Parkinson’s disease www.eurekalert.org
Parkinson’s disease is a neurodegenerative disease that causes cognitive and motor impairments. The motor complications of Parkinson’s disease occur due to the damage and death of cells in a brain region called the substantia nigra, leading to insufficient dopamine production. A new report shows how an antioxidant compound found in sesame seeds, called sesaminol, can protect cells from oxidative damage and prevent the development of Parkinson’s disease.
Oxidative stress is a main driver of cell damage and aging and is the result of normal cellular metabolism. The body produces a number of antioxidant compounds to combat this damage. The production of some of these compounds is increased by a protein called Nrf2, which can be activated by our environment.
First, the authors exposed isolated brain cells to an oxidative stressor and measured the activity of Nrf2 and production of antioxidant compounds. Next, they fed sesaminol to mice that develop a disorder similar to Parkinson’s disease for 29 days. They measured the animals' motor, digestive, and brain function compared to normal mice and Parkinson’s disease mice fed a normal diet.
The authors found that sesaminol enhanced Nrf2 activity and increased production of antioxidant enzymes in response to oxidative stress. The authors also report that, compared to both groups of the mice fed a normal diet, the Parkinson’s disease mice that were fed small amounts of sesaminol exhibited normal motor and digestive function. They also had less alpha-synuclein in their brains, a misfolded protein known to accumulate during the progression of Parkinson’s disease.
The authors concluded that sesaminol may be a suitable strategy for preventing Parkinson’s disease, noting that very small amounts of the compound can be effective in protecting cells.
[Learn more about Parkinson’s disease from Dr. Giselle Petzinger.] (https://www.foundmyfitness.com/episodes/giselle-petzinger)
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Nanoparticles in air pollution accumulate in the brains of young adults: A common denominator in neurodegenerative disease? www.sciencedaily.com
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative conditions in older adults, affecting a combined 36 million people worldwide. Evidence suggests that exposure to air pollution increases the risk of developing these diseases. Findings from a recent study demonstrate that particulate matter in air pollution accumulates in the brains of young adults and may serve as a common denominator in the pathophysiology of AD and PD.
Particulate matter in air pollution is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms or less. Ultrafine particles less than 1 microgram in diameter, referred to as nanoparticles, are often enriched in highly reactive metals such as iron, aluminum, titanium, and others. They may serve as catalysts for reactive oxygen species formation and promote protein misfolding and aggregation. Nanoparticles in air pollution are not regulated and carry many health risks. They are also present in food additives and food packaging materials.
The authors of the study documented biomarkers of AD and PD present in brainstem samples taken during the autopsies of 186 healthy children and young adults (age range, 11 months to 27 years) living in the metro area of Mexico City, a region known for its high levels of air pollution. They also conducted magnetic remanence studies to quantify the presence of metal-rich nanoparticles in the brainstem samples. Finally, using high resolution scanning and transmission electron microscopy and energy-dispersive X ray analysis, they identified the composition, location, size, and shape of nanoparticles in the substantia nigra region of a randomly chosen single sample taken from the larger group. Damage to the substantia nigra is a hallmark of PD.
They found that all of the brainstem samples contained iron-, aluminum-, and titanium-rich nanoparticles. The quantity of nanoparticles varied among the brain samples, likely due to the level and duration of exposure. The authors posited that these nanoparticles could have been acquired via both oral and respiratory routes from food sources and airborne exposures, respectively. Damage to the mitochondria, endoplasmic reticulum, and neuromelanin in the single brainstem sample correlated with the presence of iron-, aluminum-, and titanium-rich nanoparticles.
These findings suggest that exposure to nanoparticles is pervasive, with evidence confirmed as early as 11 months of age. Such exposures may put people living in urban areas where high levels of air pollutants are present at greater risk for developing AD and PD.
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Primarily thought of as a brain disorder, Parkinson's disease may have a subtype that begins in nerves outside the brain. www.sciencedaily.com
Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. It typically manifests later in life and is characterized by tremors and a shuffling gait. Findings from a recent study suggest that there are two subtypes of the disease — one originating in the brain and the other arising in the peripheral nerves outside the brain.
Parkinson’s disease is associated with the death of dopamine-producing neurons and the build-up of a misfolded protein, known as alpha-synuclein, in the brain. Diagnosis coincides with the onset of motor symptoms, which occurs when fifty percent of dopaminergic neurons are lost. However, a subset of people experience non-motor symptoms, such as constipation, depression, and sleep problems, several years before diagnosis.
Previous research suggests that the disorder arises in the brain, while other data point to its origins in the peripheral nervous system. The current study used imaging techniques to investigate whether these two lines of evidence were pointing to two disease subtypes: brain-first and body-first.
REM sleep behavior disorder (RBD) is characterized by vivid dreams and excessive movements during the rapid eye movement phase of sleep. Since RBD precedes brain changes associated with various neurological disorders, the authors of the study hypothesized it was a marker for a body-first subtype.The case-control study involved 37 people with suspected Parkinson’s disease between the ages of 50 and 85 years, and 22 people with RBD of unknown cause. The authors used video-polysomnography to divide participants into those with RBD and those without the condition. They scanned the participants' brains, along with nerves in their colons and hearts.
In some people the scans revealed that brain degeneration occurred before the colon and heart were affected, while in other people, peripheral nerves were involved before the brain’s dopaminergic cells were affected. Furthermore, the researchers observed that RBD is predictive of the body-first subtype.
These findings suggest that two subtypes of the disease exist, one originating in the brain, and one beginning in the nerves of the periphery. This hypothesis, if confirmed, has implications for the treatment of this devastating disease.
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Skin cells from a patient with Parkison's disease were transformed into stem cells that formed dopaminergic cells. www.nejm.org
Exciting news on the induced pluripotent stem cell front! Skin cells from a patient with Parkison’s disease were transformed into stem cells that formed dopaminergic progenitor cells. These dopamine-producing cells were transplanted into the patient’s brain which resulted in stabilized or improved symptoms 18-24 months later. Parkinson’s disease is the second most common neurodegenerative disease and results in a loss of dopaminergic neurons in the substantia nigra brain region causing loss of motor control, balance, and other problems. There is currently no pharmaceutical treatment that can delay the progression of Parkinson’s disease. Current treatments can help symptoms but do not delay the progression. High-intensity exercise is the only treatment that I know of that has been shown to delay the progression of this degenerative disease (more to come on this very soon). The potential to delay the progression with induced pluripotent stem cells has been emerging for several years. A pluripotent stem cell is a stem cell that can form any cell type in the body including neurons. An induced pluripotent stem cell is a stem cell that is formed from another already adult cell type usually a skin cell. This new preliminary study found that a patient’s skin cells could be used to form induced pluripotent stem cells which then were transformed into dopaminergic progenitor cells. Those dopaminergic progenitor cells were transplanted into two brain regions. Brain imaging revealed an increase in dopamine in those brain regions 18-24 months later. Clinical symptoms also stabilized or improved. This is an exciting pilot study that needs to be confirmed in larger trials!
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BDNF mimetic 7,8-dihydroxyflavone protects neurons against cell death. www.sciencedaily.com
BDNF’s neuroprotective capacity suggests that it could be useful in preventing or treating neurodegenerative diseases. Circumventing problems with BDNF’s delivery, half-life, and other limitations has proven challenging. A 2010 study found that 7,8-dihydroxyflavone, a BDNF mimetic, exerted neuroprotective qualities similar to those of BDNF.
7,8-dihydroxyflavone is a type of flavonoid compound present in a variety of plants. Flavonoids exert antioxidant and anti-inflammatory effects, among others. Some evidence indicates that 7,8-dihydroxyflavone might be useful in reversing the damage associated with lead poisoning in children.
The authors of the study screened 2,000 bioactive compounds to gauge their ability to protect rodent and human neurons from apoptosis and identified five compounds, including 7,8-dihydroxyflavone, that showed potential in protecting the cells. Then they treated the cells with BDNF and the various compounds and deprived the cells of oxygen and glucose.
They found that none of the compounds was as effective as 7,8-dihydroxyflavone in protecting the cells from apoptosis. In fact, 7,8-dihydroxyflavone was even more protective than BDNF. They also found that 7,8-dihydroxyflavone exerted its protective qualities by activating a receptor called TrkB, to which BDNF binds. They replicated their findings in an in vivo study of mice, indicating that 7,8-dihydroxyflavone enhances neuronal survival.
These findings demonstrate that flavonoid compounds that mimic the effects of BDNF show potential as therapeutics against neurodegenerative diseases.
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A disrupted sleep-wake cycle may be an early warning sign of Parkinson's disease. www.sciencedaily.com
Parkinson’s disease, or PD, is a neurodegenerative disorder identified by the death of dopamine-producing neurons in the part of the brain that controls movement. The disease typically manifests later in life and is characterized by tremors and a shuffling gait. However, other regions of the brain are also affected, and sleep disturbances are a common non-motor feature of PD. Findings from a new study suggest that a disrupted circadian rhythm is a risk factor for PD.
The circadian rhythm is the body’s 24-hour clock that modulates a wide array of physiological processes, including the production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. As such, circadian rhythmicity may have profound implications for human healthspan. The circadian rhythm changes with age and older adults have less deep, more fragmented sleep. Alterations in the circadian rhythm are more profound in people with PD, even in the early stages of the disease before symptoms develop.
Previous research in animals has demonstrated that damage to circadian-related neurons occurs during the presymptomatic stages of PD. The current study investigated whether a disordered circadian rhythm in later life is associated with an increased risk of developing PD in humans.
In a longitudinal prospective study, the authors recruited 2,930 healthy, community-dwelling older men without PD. The authors measured the rest-activity rhythms of the participants by having them wear a device on their wrist that measured activity, known as an actigraph. The authors collected recordings of activity and sleep patterns over three continuous 24 hour periods and plotted them on a graph for each participant. During the following 11 years, the men were asked if they had received a PD diagnosis and whether they were taking medications for the disease. The actigraphs revealed that participants with a less robust circadian rhythm, as evidenced by features including reduced activity and drowsiness during the day and fragmented sleep, had an increased risk of developing PD over the subsequent 11-year period.
These findings suggest that an altered circadian rhythm may occur years in advance of clinical signs of PD and might be a useful prognostic marker. Even for community-dwelling older adults, reduced daily activity, daytime drowsiness, and fragmented sleep may be signals that warrant attention. Further research is needed to determine if these findings also apply to women and younger individuals.
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higher acid-sphingomyelinase associated with disease progression in Alzheimer's www.ncbi.nlm.nih.gov
“Pharmacological restoration of ASM to the normal range improves pathology in AD mice The ASM-mediated lysosomal/autophagic dysfunction in AD prompted us to examine possible therapeutic implications of this pathway. To decrease ASM in APP/PS1 mice, we undertook pharmacological inhibition using amitriptyline-hydrochloride (AMI) for 4 mo (Fig. 9 A). AMI is a known inhibitor of ASM that can cross the blood–brain barrier. At 9 mo of age, AMI-treated APP/PS1 mice exhibited decreased ASM activity compared with vehicle-treated mice (Fig. 9 B). Other sphingolipid metabolites were not changed (Fig. 9 C). Aβ levels were decreased in the AMI-treated APP/PS1 mice compared with the nontreated littermates.”
“ASM activity is known to be increased by environmental stress and in various diseases, and is elevated in AD patients (He and Schuchman, 2012). One downstream consequence of increased ASM is elevated ceramide, contributing to cell death, inflammation, and other common disease findings. Although elevated ASM is known to occur in AD, the cellular mechanisms that link ASM and AD have not been fully characterized. The data presented here suggest a previously unknown role of ASM in the down-regulation of lysosomal biogenesis and inhibition of lysosome-dependent autophagic proteolysis. The findings also establish proof of concept for ASM inhibitor therapy in AD.”
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People with Parkinson's disease that received a growth factor (GDNF) experienced a 100% improvement in dopamine uptake in a key brain region. sciencesources.eurekalert.org
People with Parkinson’s disease that received a growth factor (GDNF) experienced a 100% improvement in dopamine uptake in a key brain region involved in the disease compared to the placebo group which did not experience any change. The participants that received GDNF also showed moderate to large improvements in symptoms.
The GDNF was implanted into the brain using robot-assisted neurosurgery. This delivery system allowed a high flow rate of GDNF infusions that were administered every four weeks.
Parkinson’s disease leads to a substantial decrease in dopamine-producing neurons in the brain. These neurons are important for motor control and other cognitive functions.
Several animal studies have identified GDNF as an important regulator of dopamine neurons in the brain. Interestingly, animal studies have also shown that GDNF is produced in the brain after acute and long-term exercise. Exercise has been shown to improve Parkinson’s disease symptoms in several clinical trials.
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Animal study demonstrates fungus C. albicans can cross the blood-brain barrier and may promote neurodegenerative disease, such as Alzheimer's www.sciencedaily.com
A common type of fungus, Candida albicans, was shown to cross the blood-brain barrier and trigger an inflammatory response in the brain that results in memory impairment (mouse study).
These findings raise the possibility that fungal infections may play a role in the development of chronic neurodegenerative disorders, such as Alzheimer’s disease. Dr. Dale Bredesen talks about this is the recent podcast episode I did with him.
Check that out here: https://www.foundmyfitness.com/episodes/dale-bredesen
From the article:
“We thought that yeast would not enter the brain, but it does,” Corry said. “In the brain, the yeast triggered the activity of microglia, a resident type of immune cell. The cells became very active ‘eating and digesting’ the yeast. They also produced a number of molecules that mediated an inflammatory response leading to the capture of the yeasts inside a granule-type structure inside the brain. We called it fungus-induced glial granuloma, or FIGG.”
The mice cleared the yeast infection in about 10 days; however, the microglia remained active and the FIGGs persisted well past this point, out to at least day 21. Intriguingly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the trademark of Alzheimer’s disease. […] Intriguingly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the trademark of Alzheimer’s disease.
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“The results prompted us to consider the possibility that in some cases, fungi also could be involved in the development of chronic neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and multiple sclerosis. We are currently exploring this possibility.”
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More than 1 serving of low-fat but not high-fat dairy per day linked to a 40% higher risk of developing Parkinson's. www.sciencedaily.com
Consuming more than one low-fat but not high-fat dairy product per day was associated with a 35-40% increased risk of developing Parkinson’s disease compared to those that had less than one serving of low-fat dairy.
The overall risk of developing Parkinson’s disease was still quite low. Out of the 5,830 trial participants that consumed low-fat dairy only 1% of developed Parkinson’s. The 77,864 people who consumed less than one serving of low-fat dairy per day only 0.6% developed Parkinson’s disease.
While this is an interesting observation (particularly since the finding was limited to low-fat dairy and not high fat), there is still much more to explore. Since this was not a controlled trial and the study did not control for other confounding factors (since it was looking at baseline characteristics) it is possible that other things associated with low-fat dairy consumption may increase Parkinson’s risk. For example, people that eat low-fat dairy products also may be more likely to consume other low-fat products, many which historically have had transfats in them. More research needs to be done before any conclusions can be made.
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Traumatic brain injury disrupts the brain's waste removal system, allowing toxic proteins to accumulate in the brain. www.sciencedaily.com
From the article:
The new research focuses on the impact that traumatic brain injury has on the glymphatic system. It has been long observed that the protein tau plays an important role in the long-term damage sustained by the brain after a trauma. Tau helps stabilize the fibers, or axons, that nerve cells send out to communicate with their neighbors.
However, during trauma, large numbers of these proteins are shaken free from the axons to drift in the space between the brain’s cells. Once unmoored from nerve cells, these sticky proteins are attracted to each other and, over time, form increasingly larger “tangles” that can become toxic to brain function.
Under normal circumstances, the glymphatic system is able to clear stray tau from the brain. However, when the researchers studied the brains of mice with traumatic brain injury, they found that the trauma damaged the glymphatic system, specifically the ability of astrocytes – a support cell found in the brain – to regulate the cleaning process.