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ABSTRACT:Since Idiopathic Parkinson's disease (IPD) was first described more than 170 years ago, there have been major advances in the understanding of the etiology of the disease as well as in its treatment. This article will review current knowledge concerning the role of the environment, genetic hypotheses and the aging factor in the etiology of IPD and proposes a complex interaction involving all these factors. Hypotheses regarding mitochondrial inhibition and free radical generation in IPD are discussed in relation to the mechanism of action of neurotoxins known to produce parkinsonian syndromes. RESUME: Depuis sa description initiale il y a un peu plus de 170 ans, de nombreuses decouvertes fondamentales et cliniques ont permis de mieux compredre la maladie de Parkinson. Cet article detaille certaines observations recentes concernant le role possible de l'environnement, la genetique et le vieillissement dans I'etiologie de la maladie de Parkinson. Les hypotheses concernant l'inhibition mitochondriale et la generation de radicaux libres dans la maladie de Parkinson sont discutees en rapport avec les mecanismes d'action de neurotoxines connues comme produisant des syndromes parkinsoniens.Can. J. Neurol. Sci. 1991; 18: 70-76 Idiopathic Parkinson's disease (IPD) is characterized by major clinical disturbances caused by dopamine depletion in the corpus striatum, resulting from neuronal loss in the substantia nigra (SN).1 The dopamine depletion is the result of a severe degeneration of the dopaminergic nigro-striatal pathway which normally inhibits the activity of a subpopulation of striatal neurons. While the physiological and neurochemical consequences of the dopamine depletion have been extensively documented, very little is known about the underlying cause of dopamine cell death or the mechanism by which dopamine cells degenerate. Numerous hypotheses have been presented including the following: a) IPD is the result of a random process.2 This hypothesis assumes that the age-related loss of neurons can be accelerated by the cumulative action of repeated insults of ordinary life (viruses, toxins, head injury, etc.). A revised form of this concept is also known as the "accelerated aging hypothesis". 3 b) IPD is the result of a lack of neurotrophic hormone. 4 It is hypothesized that a dopaminergic-specific growth factor is synthesized and stored in the target striatal cells and that the inability of these cells to provide the required dopaminergic neurotrophic hormone, thereby causes impairment to SN neurons, c) IPD is caused by a defect in the DNA repair mechanism.5 This hypothesis is derived from observations showing that cultured fibroblasts from parkinsonian patients are hypersensitive to the lethal effects of DNA-damaging agents such as x-rays. It postulates that somatic mutations occurring in early embryogenesis cause a lifelong accumulation of unrepaired DNA damage in neurons, resulting in lethal consequences on the SN. d) IPD is the result of a specific genetic defect(s) or genetic predisposition(s).3 '...