The pathology roadmap in Parkinson disease

D. James Surmeier*, David Sulzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

An under-appreciated clue about pathogenesis in Parkinson disease (PD) is the distribution of pathology in the early and middle stages of the disease. This pathological "roadmap" shows that 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, phenotypic dysregulation or frank degeneration in PD patients. This spatially distributed, at-risk population of neurons shares a number of features, including autonomously generated activity, broad action potentials, low intrinsic calcium buffering capacity and long, poorly myelinated, and highly branched axons. Many, and perhaps all, of these traits add to the metabolic burden in these neurons, suggesting that mitochondrial deficits could drive pathogenesis in PD- in agreement with a large segment of the literature. What is less clear is how this neuronal phenotype might shape the susceptibility to proteostatic dysfunction or to the spread of α-synuclein fibrils deposited in the extracellular space. The review explores the literature on these issues and their translational implications.

Original languageEnglish (US)
Pages (from-to)85-91
Number of pages7
JournalPrion
Volume7
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Calcium
  • Ion channel
  • Mitochondria
  • Neuroprotection
  • Oxidant stress
  • Parkinson disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

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