title: Neuronal vulnerability, pathogenesis, and Parkinson's disease.
abstract: Although there have been significant advances, pathogenesis in Parkinson's disease (PD) is still poorly understood. Potential clues about pathogenesis that have not been systematically pursued are suggested by the restricted pattern of neuronal pathology in the disease. In addition to dopaminergic neurons in the substantia nigra pars compacta (SNc), a significant number of other central and peripheral neuronal populations exhibit Lewy pathology (LP), phenotypic dysregulation, or frank degeneration in PD patients. Drawing on this literature, there appears to be a small number of risk factors contributing to vulnerability. These include autonomous activity, broad action potentials, low intrinsic calcium buffering capacity, poorly myelinated long highly branched axons and terminal fields, and use of a catecholamine neurotransmitter, often with the catecholamine-derived neuromelanin pigment. Of these phenotypic traits, only the physiological ones appear to provide a reachable therapeutic target at present.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sulzer
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000473:pathology*; D006801:Humans; D010300:Parkinson Disease / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*