Get access

Neuronal vulnerability, pathogenesis, and Parkinson's disease

Authors


  • 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.), NIH (P50NS38370; to D.S.), the Hartman Foundation (to D.J.S.), and the Parkinson's Disease Foundation (to D.S.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Dr. David Sulzer, 650 West 168 St., Black 305, New York, NY 10032, USA; ds43@columbia.edu

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 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

Ancillary