Premium
Neuronal vulnerability, pathogenesis, and Parkinson's disease
Author(s) -
Sulzer David,
Surmeier D. James
Publication year - 2013
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25095
Subject(s) - pars compacta , substantia nigra , neuromelanin , neuroscience , pathogenesis , parkinson's disease , dopaminergic , dopamine , locus coeruleus , disease , neurodegeneration , biology , lrrk2 , medicine , pathology , central nervous system
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 appear 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 monoamine 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. © 2013 Movement Disorder Society