Funding agencies: This work was supported by grants from the JPB Foundation (to D.S. and D.J.S.); NIH (P50NS047085 to D.J.S.; P50NS38370 to D.S.); the Hartman Foundation (to D.J.S.); and the Parkinson s Disease Foundation (to D.S.).
Neuronal vulnerability, pathogenesis, and Parkinson's disease
Article first published online: 15 APR 2013
Copyright © 2013 Movement Disorder Society
Volume 28, Issue 6, pages 715–724, June 2013
How to Cite
Sulzer, D. and Surmeier, D. J. (2013), Neuronal vulnerability, pathogenesis, and Parkinson's disease. Mov. Disord., 28: 715–724. doi: 10.1002/mds.25187
Relevant conflicts of interest/financial disclosures: D. James Surmeier has acted as a consultant to Genetech, Merck, Pfizer and Teva. Dr. Sulzer has no industry associations.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 25 JUN 2013
- Article first published online: 15 APR 2013
- Manuscript Accepted: 27 JUL 2012
- Manuscript Received: 19 JUL 2012
- Lewy body
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. © 2013 Movement Disorder Society