Determinants of dopaminergic neuron loss in Parkinson's disease

Dalton James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

The cardinal motor symptoms of Parkinson's disease (PD) are caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Alpha-synuclein (aSYN) pathology and mitochondrial dysfunction have been implicated in PD pathogenesis, but until recently it was unclear why SNc dopaminergic neurons should be particularly vulnerable to these two types of insult. In this brief review, the evidence that SNc dopaminergic neurons have an anatomical, physiological, and biochemical phenotype that predisposes them to mitochondrial dysfunction and synuclein pathology is summarized. The recognition that certain traits may predispose neurons to PD-linked pathology creates translational opportunities for slowing or stopping disease progression.

Original languageEnglish (US)
Pages (from-to)3657-3668
Number of pages12
JournalFEBS Journal
Volume285
Issue number19
DOIs
StatePublished - Oct 2018

Keywords

  • autophagy
  • axon
  • bioenergetics
  • calcium
  • dopamin
  • lewy pathology
  • mitochondria
  • synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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