Neuronal vulnerability, pathogenesis, and Parkinson's disease

David Sulzer, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

105 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)715-724
Number of pages10
JournalMovement Disorders
Volume28
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Calcium
  • Dopamine
  • Lewy body
  • Mitochondria
  • Neurodegeneration
  • Neuromelanin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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