Wednesday, November 30, 2022

Environmental Factors Causing Parkinson’s Disease

No One Definitive Cause Of Parkinsons

Environmental Factors in Parkinson’s Disease with Harvey Checkoway – On Our Mind

There are no biomarkers or objective screening tests that indicate one has Parkinsons. That said, medical experts have shown that a constellation of factors are linked to it.

Parkinsons causes are likely a blend of genetics and environmental or other unknown factors. About 10 to 20 percent of Parkinsons disease cases are linked to a genetic cause, says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering at Johns Hopkins. The types are either autosomal dominant or autosomal recessive .

But that leaves the majority of Parkinsons cases as idiopathic, which means unknown. We think its probably a combination of environmental exposure to toxins or pesticides and your genetic makeup, says Dawson.

Age. The biggest risk factor for developing Parkinsons is advancing age. The average age of onset is 60.

Gender. Men are more likely to develop Parkinsons disease than women.

Genetics. Individuals with a parent or sibling who is affected have approximately two times the chance of developing Parkinsons. Theres been an enormous amount of new information about genetics and new genes identified over the past 10 or 15 years that have opened up a greater understanding of the disease, says Dawson.

Genetic And Environmental Factors Affect Gut Microbiota

The gut microbiota is a dynamic microbial system, and it can be modified by genetic and environmental factors. Previous studies have reported that the gut microbiota is constantly challenged by environmental factors such as exercise, diet, stress, altitude, temperature, toxicants/pollutants, and noise,. Environmental contaminants can affect the composition of the gut microbiota, leading to physiological disorders in the host and causing certain diseases. The gut microbiota has become a new toxicological target for some environmental pollutants. A decreasing diversity of gut microbiota is often observed after exposure to heavy metals. In our previous studies, Mn exposure led to decreased abundances of Prevotellaceae, Fusobacteriaceae, and Lactobacillaceae,. In addition, Nasuti et al. showed that changes in gut microbiota may be one of the reasons for the neurotoxicity of permethrin. Many studies have shown that antibiotic administration leads to disturbances in the microbial diversity and metabolism of the gut microbiome that might be linked to a multitude of diseases.

Potential Causes Of Parkinsons Disease

The causes of Parkinsons disease are still unknown, although there is some evidence for the role of genetics, environmental factors, or a combination of both. It is also possible that there may be more than one cause of the disease. Scientists generally believe that both genetics and environment interact to cause Parkinsons disease in most people who have it.

Currently, there is an enormous amount of research directed at producing more answers about what causes Parkinsons disease and how it might be prevented or cured. When physicians diagnose Parkinsons, they often describe it as idiopathic . This simply means that the cause of the disease is not known.

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The Five Environmental Causes Of Parkinsons Disease

Parkinsons disease is a brain disorder that develops and becomes worse over time. The typical symptoms of the disease include tremor, stiffness, slowness of movement, and balance problems. These symptoms develop when the brain lost its ability to produce a sufficient amount of dopamine, a neurotransmitter responsible for controlled body movement.

Researchers have identified a variety of environmental factors that are linked to Parkinsons disease. Some of these factors may directly cause the disease symptoms, others may increase the risk of developing it.

Here are the 5 main environmental factors that are linked to Parkinsons disease development.

Pesticide And Herbicide Exposure

Frontiers

A strong link has been shown between PD and exposure to pesticides and herbicides. We need more Parkinsons-specific research to better understand what causes PD and to work to prevent it and help eliminate the risk of getting the disease, when it comes to all environmental risk factors and whether genetics can cause an increased risk in developing Parkinsons.

One herbicide that has been linked to Parkinsons is paraquat, a widely used commercial herbicide in the U.S. that is banned in 32 countries, including the European Union and China. The Parkinsons Foundation, along with the Unified Parkinsons Advocacy Council, signed two letters to the U.S. Environmental Protection Agency encouraging them to cancel the registration of paraquat based on strong scientific research linking the herbicide to Parkinsons disease. In October 2020, the EPA re-approved paraquat for use in the U.S. Without additional action, paraquat will remain legal for sale and use in the U.S. for the next 15 years.

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What Causes Parkinsons Disease

Parkinsons disease is a chronic, progressive neurological disease that currently affects about 1 million Americans. Parkinsons disease involves a small, dark-tinged portion of the brain called the substantia nigra. This is where you produce most of the dopamine your brain uses. Dopamine is the chemical messenger that transmits messages between nerves that control muscle movements as well as those involved in the brains pleasure and reward centers. As we age, its normal for cells in the substantia nigra to die. This process happens in most people at a very slow rate.

But for some people, the loss happens rapidly, which is the start of Parkinsons disease. When 50 to 60 percent of the cells are gone, you begin to see the symptoms of Parkinsons.

What Are Other Parkinsons Disease Risk Factors

  • Age: Parkinsons disease mainly affects people over 60 years of age and the risk of developing the disease increases over the years.
  • Population: Parkinsons disease is more common among people with white skin.
  • Sex: More men have Parkinsons disease than women.
  • Career: Some occupations, such as farmers or factory workers, may be more exposed to certain chemicals or toxins that increase the risk of developing Parkinsons disease.
  • Serious head injuries: Different types of serious head and brain injuries, such as concussions, increase the risk of developing the disease.
  • Location: The number of people living with the disease in rural areas is higher. This seems to be related to agricultural pesticide exposure.

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Other Causes Of Parkinsonism

“Parkinsonism” is the umbrella term used to describe the symptoms of tremors, muscle rigidity and slowness of movement.

Parkinson’s disease is the most common type of parkinsonism, but there are also some rarer types where a specific cause can be identified.

These include parkinsonism caused by:

  • medication where symptoms develop after taking certain medications, such as some types of antipsychotic medication, and usually improve once the medication is stopped
  • other progressive brain conditions such as progressive supranuclear palsy, multiple systems atrophy and corticobasal degeneration
  • cerebrovascular disease where a series of small strokes cause several parts of the brain to die

You can read more about parkinsonism on the Parkinson’s UK website.

Page last reviewed: 30 April 2019 Next review due: 30 April 2022

The Search For Environmental Causes Of Parkinson’s Disease Moves Forward

Parkinson’s Disease Etiology | Environmental factors | Genetic factors |
Date:
IOS Press
Summary:
Scientists evaluate promising research hypotheses for understanding environmental triggers in Parkinson’s disease and propose future directions for research.

Environmental factors are widely believed to play a key role in the development of Parkinson’s disease , but little is known about specific environmental triggers. Writing in the Journal of Parkinson’s Disease, scientists review novel research hypotheses and approaches that may help better define the role of environment in the development of PD, especially before a diagnosis can be made based on the characteristic motor dysfunction for which PD is known.

Late-onset sporadic PD takes decades to develop, and by the time of diagnosis, some of the neurodegenerative changes are too advanced to slow down, stop, or reverse. On the other hand, environmental factors that cause or trigger its development and modify its progression may come into play during the “prodromal phase,” decades before specific signs and symptoms develop. “This prodromal stage is of major interest for prevention efforts,” explained the authors. “Targeting factors that enter the body via the nose or gut has become even more important since the discovery that the alpha-synuclein protein-related Lewy pathology, which is characteristic of PD, was identified in the nervous systems of the olfactory pathway and the digestive tract.”

Braak Hypothesis

Story Source:

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Genetic And Environmental Risk Factors For Neurodegenerative Diseases

Mutations in the gene encoding leucine-rich repeat kinase 2 are the most common cause of hereditary PD. LRRK2 activity promotes -synuclein propagation via the phosphorylation of RAB35. A genetic component for the apparently sporadic disease was not obvious in the early days of PD research. LRRK2 mutations can cause familial PD with age-dependent but variable penetrance variants of the gene are also risk factors for sporadic PD. Individuals with mutations in the genes PARKIN, PINK1, SNCA, GBA1, and LRRK2 show an increased risk of developing familial PD . In addition, multiple mutations in genes such as C9orf72, TARDBP, and SOD1 are mainly expressed in a variety of nonneuronal cells which enhance immune dysregulation and neuroinflammation in the pathogenesis of ALS.

Fig. 3: Implications of metals in A neurotoxicity.

APP binds to metals . Under acceleratory conditions, A self-aggregates and forms several types of oligomers finally forming insoluble aggregates , and tight binding to the surface of neurons and form fibrillar deposits.

Advancing Age And Parkinsons Disease

Age is perhaps the biggest risk factor for the onset of Parkinsons disease. The average age at which people will develop this movement disorder is 60. This is not usually something that affects younger people. The brain ages as people get older.

Even without external factors, cells in the substantia nigra can die on their own as an individual ages, causing symptoms to develop as the person gets older.

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How Do Genetics Contribute To The Development Of Parkinsons Disease

Genes are like an instruction manual. They code the synthesis of molecules that make up the body. A change in these instructions can lead to different effects and potentially to diseases.

Some of these modifications or mutations have been identified in people living with Parkinsons disease. They increase the risk of developing the disease but are not common. Moreover, they do not always lead to the development of the disease.

Snp Selection And Genotyping

Frontiers

Thirteen SNPs that have been associated with PD in at least one out of the 5 large GWAS meta-analysis studies for PD in the European population were selected for genotyping . The selection criteria for the SNPs were based on the estimates of the association and on the frequency of the minor allele , in order to ensure the maximum statistical power for their investigation. There was an estimation of the power of the study at a value of 0.05 to detect ORs similar to those previously reported in the GWAS, given the allele frequencies observed in the Cypriot population.

DNA was extracted from peripheral blood lymphocytes as described elsewhere . SNP genotyping was performed using Taqman genotype assays . Each assay was carried out using 10 ng genomic DNA in a 5 μl reaction using Taqman Universal PCR Master Mix . The fluorescence profile was read on an ABI PRISM 7900HT instrument and the results analyzed with Sequence Detection Software .

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Environmental Factors: Etiological And Disease

From 1817 when Dr. James Parkinson first described 6 patients with the condition that would later bear his name , much progress was made in the following 150years. It became known that the SN was the site affected by PD pathology together with the presence of cytoplasmic inclusions, and levodopa became available as the first effective symptomatic drug treatment of PD in 1960s . However, the etiology of PD remained elusive.

Table 1 Examples of environmental factors and their biologic correlates

The most robust beneficial environmental factor associated with PD is cigarette smoking which has been seen in early case-control studies and then confirmed in more recent large prospective cohorts. Active smokers have 50% lower risk of PD compared to never smokers . There is a strong dose-response relationship including duration, intensity, pack-years and years since last smoking: PD risk decreases with increasing duration of smoking and increases again with time since quitting . Preliminary reports also support an inverse relationship between passive smoking, smokeless tobacco use and PD .

How You Lose Dopamine Production

Damaged nerve cells can be what results in a decreased ability of the brain to create dopamine. Generally, some kind of degradation of the brain cells will reduce dopamine production.

There is some genetic link to parkinsons disease. For example, specific genetic mutations can impact the dopamine production. Far more common is that exposure to something in the environment can impact the brain.

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Fecal Microbiota Transplantation In Neurodegenerative Diseases

Germ-free wild-type mice and their offspring had ASD-like symptoms and displayed alternative splicing of ASD-relevant genes when FMT was performed with stool from children with ASD. ASD symptoms decreased when GABA receptor agonists were administered to the ASD model. Decreased cerebral oxidative stress was observed in another study after FMT from a normal hamster in an ASD hamster model.

FMT may reverse the decrease in cognitive function induced by antibiotics. Wild-type mice showed a cognitive decline after broad-spectrum antibiotic therapy. However, memory and spatial learning were improved after receiving anti-aging mouse feces. Human microbiome transplantation protected germ-free mice from death caused by acute arsenic toxicity. According to our research, Mn exposure increased A and inflammatory factor production in the brain and caused hippocampal degeneration and necrosis,. FMT from normal rats alleviated the neurotoxic effects of Mn exposure by altering the gut microbiota.

Environmental Factors In Parkinsons Disease

Environmental Factors With Parkinson’s Disease – Ask The Doctor

Here are environmental factors that may play a role in the development of Parkinsons disease:

Although environmental exposure to these and other toxins is of continued research interest, its hard to determine if any one substance is a culprit. Most often, individual cases of Parkinsons disease result from a complex interplay between genetics and environmental and other factors.

Targeting Parkinsons-Linked Protein Could Neutralize 2 of the Diseases Causes

Researchers report they have discovered how two problem proteins known to cause Parkinsons disease are chemically linked, suggesting that someday, both could be neutralized by a single drug designed to target the link.

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Is Parkinsons Disease Hereditary

Hereditary diseases are passed from parents to their children, but cases of familial Parkinsons disease are very rare . The vast majority of Parkinsons cases are not transmissible.

Having Parkinsons disease does not affect your childrens risk of developing the disease. Similarly, your risk is not increased if your brother or sister has the disease. However, your risk may be increased if more than one person in your family has the disease.

Exposure to certain environmental factors or toxins may contribute to the development of Parkinsons disease.

The main environmental factors involved in Parkinsons disease are:

Want To Learn More About The Latest Research In Parkinsons Disease Ask Your Questions In Our Research Forum

Environmental factors may trigger Parkinsons or modify its progression during the prodromal stage, in which early symptoms or signs are present, but clinical diagnosis is not yet possible. Among the reported factors, smoking, coffee, exercise, plasma urate, and use of ibuprofen have been linked to a lower risk of Parkinsons, while pesticide exposure and traumatic brain injury have been associated with a greater risk.

Apart from two pesticides known as rotenone and paraquat, researchers have had difficulties in providing evidence that other risk factors can cause the disease. Reverse causation meaning that Parkinsons changes lifestyle and behavior before a clinical diagnosis rather than the other way around has been proposed as an explanation for the link between these environmental triggers and Parkinsons in its early stages.

This prodromal stage is of major interest for prevention efforts, the researchers said in the release, adding that the discovery of Lewy bodies protein aggregates mainly composed of alpha-synuclein that are characteristic of Parkinsons in the olfactory pathway and the digestive tract made targeting factors that enter the body via the nose or gut even more important.

We are at an exciting moment to unveil environmental contributions to development and progression by taking a life-course approach, and utilizing novel tools to assess environmental exposures, the researchers said.

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Genetics: Insights Into Etiology

Improvement in genetic analysis techniques in the 1990s led to the discovery of the first genetic cause of PD: mutations in the SNCA gene encoding -synuclein . At around the same time, -synuclein was found to be the major constituent of LB, the pathological hallmark of PD . Subsequently, multiplications of the SNCA gene have been found to cause PD with penetrance increasing with gene dosage . These discoveries brought -synuclein to center stage in the study of the pathogenesis of PD and led to the hypothesis that during different stages of the disease, -synuclein spreads in a stereotypical way within the nervous system in a prion-like fashion .

Table 2 Examples of genes associated with PD risk

What Causes Parkinsons

Schematic presentation of neuronal death in Parkinson

Parkinsons is a disease of the central nervous system caused by the loss of dopamine-producing cells in the brain. However, exactly why dopamine-producing cells become lost is unclear. Research suggests that a combination of genetic and environmental factors may be responsible. How these two factors interact varies from person to person. It is also unclear why some people develop the disease but not others.

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