Frontiers in Neuroscience (Jan 2016)

Is alpha-synuclein loss-of-function a contributor to parkinsonian pathology? Evidence from non-human primates

  • Timothy J Collier,
  • D Eugene Redmond,
  • Kathy eSteece-Collier,
  • Jack W Lipton,
  • Fredric P Manfredsson

DOI
https://doi.org/10.3389/fnins.2016.00012
Journal volume & issue
Vol. 10

Abstract

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Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson’s disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of nonhuman primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.

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