Vulnerability to Parkinson's Disease: Towards an Unifying Theory of Disease Etiology

Interactions between genes and environmental factors critically modulate individual’s healthy and diseasedstates, including the vulnerability to certain major neurologicdisorders such as Parkinson’s disease (PD). PD isthe most common neurodegenerative disorder affectingapproximately 1% of the population over age 65. Althoughmost cases of PD are observed later in life, thereis evidence that the disease has progressed to the point atwhich it is diagnosed. PD is of unknown origin butpresumably of multifactorial etiology. Several genes thatcause certain forms of inherited PD (o10% cases) havebeen identified, but the majority of cases (490%) appearto be sporadic and are likely to represent an interplaybetween genetic and environmental influences. Moremen than women develop PD; aging and menopause inwomen (estrogen deficiency) are the recognized riskfactors. Polymorphisms in candidate genes involved indopamine metabolism, mitochondrial function, lipoproteinmetabolism, inflammation, and xenobiotic detoxificationhave been described. Living in rural areas,pesticides and heavy metals exposures, head injury, andinfectious diseases during childhood have also beensuggested to increase the risk; whereas smoking andconsumption of coffee, dietary factors, exercising andsocial interactions, or the use of certain nonsteroidal antiinflammatorydrugs (NSAIDs) reportedly reduce theincidence/risk and severity of PD.