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Etiology of Parkinson's Disease

Published online by Cambridge University Press:  02 December 2014

A. Jon Stoessl
A. Jon Stoessl*
Affiliation:
Neurodegenerative Disorders Centre, Vancouver Hospital & Health Sciences Centre, Vancouver, British Columbia
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Abstract

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Controversy over the etiology and pathogenesis of Parkinson's disease (PD) has continued for many years and while the details have changed, the uncertainty persists. Although heritability was most emphatically refuted a decade ago by many investigators, recent progress firmly indicates that genetic factors at least play a role, although probably to a variable degree from one individual to another. Evidence for a variety of other etiological factors is amassed from epidemiological studies, animal models, molecular and cellular biology. Genetic factors, infectious and immunological abnormalities, the effects of ageing, toxins (endogenous as well as exogenous) and other environmental factors may all contribute to the development of PD. Loss of nigral dopaminergic neurons may be mediated by varying combinations of oxidative free radical toxicity, impaired mitochondrial function, “weak excitotoxicity” and abnormal handling of cytoskeletal proteins, all of which may shift the balance regulating apoptotic cell death.

Résumé

RÉSUMÉ

La controverse entourant l'étiologie et la pathogenèse de la maladie de Parkinson (MP) dure depuis plusieurs années et, bien que les détails ont changé, l'incertitude persiste. Bien que l'héritabilité de la maladie ait été réfutée avec emphase par plusieurs investigateurs il y a une dizaine d'années, des progrès récents indiquent clairement que des facteurs génétiques sont en cause, probablement à des degrés variables d'un individu à l'autre. Des données sur une variété d'autres facteurs étiologiques, provenant d'études épidémiologiques, de modèles animaux, de la biologie moléculaire et cellulaire, s'accumulent. Les facteurs génétiques, anomalies infectieuses et immunologiques, les effets du vieillissement, les toxines (endogènes et exogènes) et les autres facteurs environnementaux peuvent contribuer au développement de la MP. La perte de neurones dopaminergiques dans la substance noire peut être médiée par différentes combinaisons d'effets toxiques oxydatifs dus à des radicaux libres, une fonction mitochondriale altérée, une “faible excitotoxicité” et un métabolisme anormal des protéines du cytosquelette, qui peuvent tous déséquilibrer la régulation de la mort cellulaire par apoptose.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 26 , Issue S2 , August 1999 , pp. S5 - S12
Copyright
Copyright © The Canadian Journal of Neurological 1999

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