Determinants of dopaminergic neuron loss in Parkinson's disease

FEBS J. 2018 Oct;285(19):3657-3668. doi: 10.1111/febs.14607. Epub 2018 Aug 14.


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.

Keywords: autophagy; axon; bioenergetics; calcium; dopamin; lewy pathology; mitochondria; synuclein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology*
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Oxidative Stress*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein
  • Calcium