Causes of Parkinson’s Disease

Parkinson’s disease is a progressive neurodegenerative disorder best known for its movement-related symptoms. However, it also causes cognitive changes.

Parkinson’s underlying cause is the death of dopamine-producing (dopaminergic) neurons, or nerve cells, in a brain region called the substantia nigra.

Dopamine is a neurotransmitter, which is a molecule produced by the body to send messages between nerve cells. It is involved in a range of behaviors, including control of body movements, learning and memory, the sleep-wake cycle, and moods, such as depression and mania.

Both genetic and environmental factors appear to influence a person’s risk of developing Parkinson’s. That’s why the disorder is thought to be a product of a combination of these factors. “Genetics loads the gun and environment pulls the trigger,” is one way Parkinson’s has been described.

Parkinson’s genetic factors

Although certain genes associate strongly with Parkinson’s, most cases occur in people with no obvious family history of the disorder. Only about 15–25% of patients have a known relative with the disease.

LRRK2 and SNCA are genes with strong links to Parkinson’s disease. LRRK2 provides instructions to make the leucine-rich repeat kinase 2 enzyme, which is associated with late-onset Parkinson’s. SNCA enables production of the alpha-synuclein protein that accumulates in toxic clumps, often called Lewy bodies, inside nerve cells of people with Parkinson’s. Mutations in this gene occur in early-onset Parkinson’s disease.

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Disease-causing mutations in these genes are inherited in what is called an autosomal dominant manner, meaning that only one copy — people generally receive at least one copy of a gene from each parent — is needed to trigger disease.

PARK7PINK1, and PARK2 also instruct the production of proteins that are relevant to Parkinson’s disease when they malfunction. Unlike LRRK2 and SNCA, however, they act in an autosomal recessive manner, meaning that a person would need to inherit a mutated copy from each parent in order to develop the disorder.

Mutations in other genes are associated with higher risks for developing Parkinson’s, although their precise roles are less clear. These include GBA, which orders production of the glucocerebrosidase enzyme, and UCHL1, which generates an esterase enzyme.

Environmental factors

Environmental risk factors influencing Parkinson’s range from past physical trauma to air pollutants, with no single factor clearly triggering disease onset.

Age is one of Parkinson’s more significant environmental risk factors. The disorder typically begins later in life, with most cases beginning around age 60.

Sex also affects one’s likelihood of developing the disorder, as it affects men more often than women.

Studies suggest that traumatic brain injury (TBI) — with or without the loss of consciousness — can raise the risk of developing Parkinson’s years after the injury. Studies suggest these injuries may cause inflammation in the brain, which could lead to developing the disease. Although relatively small, TBI represents a modifiable risk, in that it largely can be avoided.

Environmental toxins, such as air pollutants, pesticides, and some metals, form an area of active research into possible causes of Parkinson’s.

Several studies have identified associations between areas of higher air pollution and clusters of Parkinson’s, wherein the disorder is diagnosed at higher-than-expected rates. Exactly how pollutants might trigger Parkinson’s remains unclear, however, and not all studies support these as causes of the disease.

Similarly, several occupations, such as welders, that involve exposure to fine metal particulates, appear to raise the risk of Parkinson’s. Again, however, the results of studies on this topic have been inconsistent.

Certain pesticides, fungicides, and herbicides — Agent Orange and paraquat notable among them — have attracted scientific attention for their associations with Parkinson’s. Paraquat’s possible contribution to the disorder remains actively debated, and in 2009 the U.S. Department of Veterans Affairs added Parkinson’s to the list of disorders possibly associated with Agent Orange exposure.

Other agricultural toxins under investigation for potential links to Parkinson’s include maneb, permethrin, beta-hexachlorocyclohexane, and dichlorophenoxyacetic acid.

Parkinson’s-like symptoms

Certain drugs, brain conditions, and other diseases can trigger Parkinson’s-like symptoms.

The neurotoxin MPTP was discovered as a cause of motor symptoms similar to Parkinson’s in the 1980s and became the focus of more than one medical detective story. The compound now is used regularly to create mouse models of Parkinson’s disease.

Certain antipsychotic medications also can cause Parkinson’s symptoms. Whereas MPTP’s effects are irreversible, those of antipsychotics generally fade after the medication is stopped.

Multiple systems atrophy, Lewy body disease, progressive supranuclear palsy, and other brain conditions often mimic the symptoms of Parkinson’s.

Finally, cerebrovascular diseases such as stroke can resemble aspects of Parkinson’s, by damaging and often killing some parts of the brain.

 

Last updated: July 8, 2021

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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