Environment, mitochondria, and Parkinson's disease.
Parkinson's disease (PD) is a common and disabling neurodegenerative disease marked by progressive motor dysfunction, which results from selective degeneration of the nigrostriatal pathway. Epidemiological studies indicate that exposure to pesticides, rural living, farming, and drinking well water are associated with an increased risk of developing PD. Rare cases of PD are caused by mutations in nuclear genes, and there is increasing evidence for susceptibility genes that alter disease risk. Parkinson's disease is also associated with a systemic defect in mitochondrial complex I activity. Animal models indicate that exposure to inhibitors of mitochondrial complex I, including pesticides, is sufficient to reproduce the features of PD, but genetic factors clearly modulate susceptibility. Complex I defects may result in oxidative stress and increase the susceptibility of neurons to excitotoxic death. In this way, environmental exposures and mitochondrial dysfunction may interact and result in neurodegeneration.
Sherer
Todd B
TB
Department of Neurology, Emory University, Atlanta, Georgia 30322, USA.
Betarbet
Ranjita
R
Greenamyre
J Timothy
JT
D000818:Animals; D042967:Electron Transport Complex I; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism; D010575:Pesticides / Q000009:adverse effects; D012307:Risk Factors
D010575:Pesticides; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I