Parkinson’s disease is caused by the impairment or death of dopamine-producing nerve cells (neurons) in a region of the brain called the substantia nigra, which controls the body’s balance and movement.
Dopamine is a chemical that acts as a messenger transmitting nerve signals from one neuron to another in the brain to control body movements. It also is involved in behavior and cognition, memory and learning, sleep, and mood. The loss of these neurons results in decreased dopamine, leading to abnormal brain activity and the symptoms of the disease, such as abnormal muscle movements and cognitive impairment.
Recent studies also have shown that Parkinson’s disease patients may have damaged nerve endings that produce norepinephrine, a signal messenger similar to dopamine that controls body functions such as pulse and blood pressure. This may explain some of the non-motor symptoms of the disease, such as fatigue and blood pressure problems.
The symptoms of Parkinson’s disease appear only when about 80 percent of nerve cells in the substantia nigra have been lost. It is thought that a combination of genetic and environmental factors contribute to the development of the disease.
In most cases, Parkinson’s disease is not inherited. However, about 15 to 25 percent of patients have a family history of the disease. People with family history of a parent or sibling having the disease, have a 3 percent lifetime risk of developing Parkinson’s disease, compared to those in the general population, who have a 1.5 percent lifetime risk.
Mutations in certain genes, such as SNCA that encodes for the protein alpha-synuclein, have been identified as inheritable and can cause the disease directly. However, those are rare except in cases where many family members are affected by the disease.
Parkinson’s disease also has been associated with mutations in genes such as PRKN, which encodes for the parkin protein, PINK1, which encodes for a protein found in the heart and skeletal muscles, LRRK2, which codes for a brain protein called dardarin, and PARK7, which encodes for a brain protein called DJ-1.
In addition, mutations in certain other genes, including GBA, which encodes for an enzyme called glucocerebrosidase, and UCHL1, which encodes for an esterase enzyme, appear to increase the risk of developing Parkinson’s disease.
Some gene mutations disturb the protein degradation machinery in the nerve cell, causing the accumulation of toxic proteins leading to cell death. Other mutations affect the function of mitochondria, the cellular structures that produce energy. As a result, free radicals produced by mitochondria accumulate, causing nerve cell damage.
In most cases, protein deposits called Lewy bodies appear in dead or dying nerve cells. However, it is unclear whether Lewy bodies cause nerve cell death or if they are formed as a result of cells’ response to the disease.
Genetics is currently the subject of intense research to better understand the causes of Parkinson’s disease.
Exposure to certain toxins or environmental triggers also may increase the risk of Parkinson’s disease, but the risk is relatively small.
Age – Parkinson’s disease usually begins in middle or late life, and the risk increases with age. About 1 percent of people older than 60 years have Parkinson’s disease, compared to just 0.001 percent of people 45 or younger.
Gender – Parkinson’s disease is more common in men than in women. It is not known whether this is due to genetic factors, hormones, or differences in behavior.
Head injury – Traumatic brain injury that results in amnesia or loss of consciousness has been associated with an increased risk of developing Parkinson’s disease years after the injury. Studies suggest that such injury may cause inflammation in the brain, which could lead to the development of Parkinson’s disease.
Exposure to toxins – Exposure to industrial pollution, herbicides (such as paraquat and dichlorophenoxyacetic acid), fungicides (maneb), and insecticides (permethrin and beta-hexachlorocyclohexane) may increase the risk of developing Parkinson’s disease. In 2009, the U.S. Department of Veteran Affairs added Parkinson’s disease to the list of diseases possibly associated with exposure to Agent Orange, a herbicide used during the Vietnam War. A synthetic neurotoxic agent called MPTP also can cause immediate and permanent Parkinsonism. MPTP was discovered in the 1980s in individuals who injected themselves with a synthetic form of heroin contaminated with MPTP. Cases of MPTP-induced Parkinson’s in the general population are very rare.
Area of residence – Some studies suggest there are differences in the geographic distribution of Parkinson’s disease, which may arise due to differences in environment or genetic factors. For example, the Inuit population in Denmark has a higher prevalence of Parkinson’s disease compared to other Danes, possibly reflecting a higher dietary intake of persistent organic pollutant such as polychlorinated biphenyls (PCB).
Occupation – Certain occupations have been associated with a higher risk of Parkinson’s disease, but the results have been inconsistent. In some reports, welding has been suggested to cause Parkinson’s disease.
Several factors may trigger Parkinson-like symptoms. These include:
Drugs – The symptoms of Parkinson’s disease may develop after taking certain medications, such as some types of antipsychotic medication, and usually improve after the medication is stopped.
Progressive brain conditions – Certain brain conditions, such as progressive supranuclear palsy, multiple systems atrophy, and corticobasal degeneration, may cause Parkinson’s disease symptoms.
Cerebrovascular disease – A series of small strokes may cause several parts of the brain to die.
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