Parkinson's disease occurs when nerve cells, or neurons,
in an area of the brain known as the substantia nigra die or become
impaired. Normally, these neurons 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 Parkinson's patients have lost 60 to 80 percent or more of the
dopamine-producing cells in the substantia nigra by the time symptoms appear.
Recent studies have shown that people with Parkinson Disease 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 help explain several of the non-motor features
seen in Parkinson Disease, including fatigue and abnormalities of blood pressure regulation.
Many brain cells of people with
Parkinson Disease contain Lewy bodies
– unusual deposits or clumps of the protein alpha-synuclein, along with
other proteins. Researchers do not yet know why Lewy bodies form or what
role they play in development of the disease. The clumps may prevent the
cell from functioning normally, or they may actually be helpful, perhaps by
keeping harmful proteins "locked up" so that the cells can function.
Scientists have identified several genetic mutations
associated with Parkinson Disease, and many more genes have been tentatively linked to the
disorder. Studying the genes responsible for inherited cases of
Parkinson Disease 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 Parkinson Disease.
Although the importance of genetics in
Parkinson Disease is
increasingly recognized, most researchers believe environmental exposures
increase a person's risk of developing the disease. Even in familial cases,
exposure to toxins or other environmental factors may influence when
symptoms of the disease appear or how the disease progresses. There are a
number of toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, or MPTP (found in some kinds of synthetic heroin), that can cause parkinsonian
symptoms in humans. Other, still-unidentified environmental factors also
may cause Parkinson Disease in genetically susceptible individuals.
Viruses are another possible environmental trigger for
Parkinson Disease. People who developed encephalopathy after a 1918 influenza epidemic were
later stricken with severe, progressive Parkinson's-like symptoms. A group
of Taiwanese women developed similar symptoms after contracting herpes virus
infections. In these women, the symptoms, which later disappeared, were
linked to a temporary inflammation of the substantia nigra.
Several lines of research suggest that mitochondria may
play a role in the development of Parkinson Disease. Mitochondria are the energy-producing
components of the cell and are major sources of free radicals — molecules
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 brains of Parkinson Disease patients.
Other research suggests that the cell's protein
disposal system may fail in people with Parkinson Disease, 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 Parkinson Disease may contribute to the death of neurons, and that inflammation or overstimulation of cells (because of toxins or other factors) may play a
role in the disease. However, the precise role of the protein deposits
remains unknown. Some researchers even speculate that the protein buildup
is part of an unsuccessful attempt to protect the cell. While mitochondrial
dysfunction, oxidative stress, inflammation, and many other cellular
processes may contribute to Parkinson Disease, the actual cause of the dopamine cell death
is still undetermined.
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