Search For Environmental Or Endogenous Neurotoxins Related To MPTP

Abstract

The cause of Parkinson’s disease remains unknown despite clinical investigations of infectious, genetic, or other contributory etiologic factors (1). Neurotoxins have been considered as causative agents in past clinical investigations due particularly to the observations of parkinsonian symptomatology caused by manganese, 6-hydroxydopamine, neuroleptics, carbon monoxide, and carbon disulfide (2). The clinical responses to each of these neurotoxins differed distinctly from Parkinson’s disease, and thus when MPTP-induced neurotoxicity was first observed (3,4), it generated considerable interest because it closely paralleled the idiopathic disease condition in nearly every aspect. MPTP-induced parkinsonism in non-human primates differs from the idiopathic disease in humans only in its rapid course, the apparent lack of progression following the toxic insult, the absence of the neuropathological hallmark Lewy bodies, and the limited involvement of neurons other than the nigro-striatal in MPTP-affected animals (5). These observations have reawakened interest in a neurotoxic etiology of Parkinson’s disease and have enabled us to define new stategies and tools for these investigations.