Parkinson's disease (PD) is a degenerative disorder of the central nervous system that belongs to a group of conditions called movement disorders. It is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. As nerve cells (neurons) in parts of the brain become impaired or die, people may begin to notice problems with movement, tremor, stiffness in the limbs or the trunk of the body, or impaired balance. As these symptoms become more pronounced, people may have difficulty walking, talking, or completing other simple tasks. Not everyone with one or more of these symptoms has PD, as the symptoms appear in other diseases as well.

The precise cause of PD is unknown, although some cases of PD are hereditary and can be traced to specific genetic mutations. Most cases are sporadicthat is, the disease does not typically run in families. It is thought that PD likely results from a combination of genetic susceptibility and exposure to one or more unknown environmental factors that trigger the disease.

PD is the most common form of parkinsonism[1], in which disorders of other causes produce features and symptoms that closely resemble Parkinsons disease. While most forms of parkinsonism have no known cause, there are cases in which the cause is known or suspected or where the symptoms result from another disorder.

No cure for PD exists today, but research is ongoing and medications or surgery can often provide substantial improvement with motor symptoms.

[1] Words in italics appear in a Glossary at the end of this information.

Parkinson's disease occurs when nerve cells, or neurons, in the brain die or become impaired. Although many brain areas are affected, the most common symptoms result from the loss of neurons in an area near the base of the brain called the substantia nigra. Normally, the neurons in this area produce an important brain chemical known as dopamine. Dopamine is a chemical messenger responsible for transmitting signals between the substantia nigra and the next "relay station" of the brain, the corpus striatum, to produce smooth, purposeful movement. Loss of dopamine results in abnormal nerve firing patterns within the brain that cause impaired movement. Studies have shown that most people with Parkinson's have lost 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra by the time symptoms appear, and that people with PD also have loss of the nerve endings that produce the neurotransmitter norepinephrine. Norepinephrine, which is closely related to dopamine, is the main chemical messenger of the sympathetic nervous system, the part of the nervous system that controls many automatic functions of the body, such as pulse and blood pressure. The loss of norepinephrine might explain several of the non-motor features seen in PD, including fatigue and abnormalities of blood pressure regulation.

The affected brain cells of people with PD contain Lewy bodiesdeposits of the protein alpha-synuclein. Researchers do not yet know why Lewy bodies form or what role they play in the disease. Some research suggests that the cells protein disposal system may fail in people with PD, causing proteins to build up to harmful levels and trigger cell death. Additional studies have found evidence that clumps of protein that develop inside brain cells of people with PD may contribute to the death of neurons. Some researchers speculate that the protein buildup in Lewy bodies is part of an unsuccessful attempt to protect the cell from the toxicity of smaller aggregates, or collections, of synuclein.

Genetics. Scientists have identified several genetic mutations associated with PD, including the alpha-synuclein gene, and many more genes have been tentatively linked to the disorder. Studying the genes responsible for inherited cases of PD can help researchers understand both inherited and sporadic cases. The same genes and proteins that are altered in inherited cases may also be altered in sporadic cases by environmental toxins or other factors. Researchers also hope that discovering genes will help identify new ways of treating PD.

Environment. Exposure to certain toxins has caused parkinsonian symptoms in rare circumstances (such as exposure to MPTP, an illicit drug, or in miners exposed to the metal manganese). Other still-unidentified environmental factors may also cause PD in genetically susceptible individuals.

Mitochondria. Several lines of research suggest that mitochondria may play a role in the development of PD. Mitochondria are the energy-producing components of the cell and abnormalities in the mitochondria are major sources of free radicalsmolecules that damage membranes, proteins, DNA, and other parts of the cell. This damage is often referred to as oxidative stress. Oxidative stress-related changes, including free radical damage to DNA, proteins, and fats, have been detected in the brains of individuals with PD. Some mutations that affect mitochondrial function have been identified as causes of PD.

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Parkinson's Disease: Hope Through Research: National ...