Parkinson's disease

Parkinson's disease (PD; paralysis agitans; also known as Parkinson disease in the U.S.) is a neurodegenerative disease of the substantia nigra, an area in the basal ganglia of the brain. The disease was first recognised and its symptoms documented in 1817 in An Essay on the Shaking Palsy by the British physician Dr James Parkinson; the associated biochemical changes in the brain of patients were identified in the 1960s. Some gene defects associated with the disease were identified only recently; others remain unknown. more...

The disease involves a progressive disorder of the extrapyramidal system, which controls and adjusts communication between neurons in the brain and muscles in the human body. It also commonly involves depression and disturbances of sensory systems.

Parkinson's disease is widespread, with a prevalence estimated between 100 and 250 cases per 100,000 in North America; globally prevalence estimates range from a low of 15 per 100,000 in China to a high of 657 per 100,000 in Argentina. Because prevalence rates can be effected by socio-ecomically driven differences in survival, incidence is a more sensitive indicator: rates have ranged from 1.5 per 100,000 in China to a high of 14.8 per 100,000 in Finland.

About 2% of the population develops the disease some time during life, though the mean age at onset is 58-60. Symptoms usually begin in the upper extremities, and are usually unilateral (one-sided) or asymmetrical at onset.

Debate over Causes: A Complex Etiology is Probable

The cause of Parkinson's disease is not known (idiopathic). There are, however, many theories.

Genetic

Geneticists have, since 1997, found nine different specific genetic defects, each of which causes the disease in one or a few families with extraordinarily high incidences of the disease, but such families are rare.

While a strong inheritance pattern occurs in only a very small percentage of cases, an affected individual is three to four times more likely than an unaffected individual to have a close relative with Parkinson's. Having a parent with Parkinson's raises one's lifetime risk of developing the disorder threefold, from the general population's figure of 2% to about 6%. Genes that have been identified include SNCA (protein alpha-synuclein), UCHL1 (protein ubiquitin carboxy-terminal hydrolase L1), PARK2 (protein parkin), "PARK6" (protein PINK1), PARK7 (protein DJ-1), and PARK7 (protein Dardarin or LRRK2). Indeed, recent linkage studies excluded most of the above gene defects from consideration in the causation of sporadic (i.e. non-familial) Parkinson's disease, which constitutes more than 95% of cases. Most recently, a new gene was identified, ND5, mutation in which is thought to account for a vast majority of sporadic PD cases (see below).

Toxins

One theory holds that the disease may result in many or even most cases from the combination of a genetically determined vulnerability to environmental toxins along with exposure to those toxins. This is argued to be consistent with the fact that Parkinson's disease is not distributed homogenously throughout the population: rather, its incidence varies geographically. The toxins most strongly suspected at present are certain pesticides and industrial metals. MPTP is used as a model for Parkinson's as it can rapidly induce parkinsonian symptoms in human beings and other animals, of any age. Other toxin-based models employ paraquat (a herbicide) in combination with maneb, a fungicide rotenone (an insecticide), and specific organochlorine pesticides including dieldrin and lindane . Studies have found an increase in PD in persons exposed to these agricultural chemicals; the risk apparently rises with exposure.

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