Animal models of α-synucleinopathy for Parkinson disease drug development

Nat Rev Neurosci. 2017 Sep;18(9):515-529. doi: 10.1038/nrn.2017.75. Epub 2017 Jul 13.


A major challenge in Parkinson disease (PD) will be to turn an emerging and expanding pipeline of novel disease-modifying candidate compounds into therapeutics. Novel targets need in vivo validation, and candidate therapeutics require appropriate preclinical platforms on which to define potential efficacy and target engagement before advancement to clinical development. We propose that α-synuclein (α-syn)-based mammalian models will be crucial for this process. Here, we review α-syn transgenic mouse models, viral vector models of α-syn overexpression and models of 'prion-like' spread of α-syn, and describe how each of these model types may contribute to PD drug discovery. We conclude by presenting our opinion on how to use a combination of these models through the late-stage preclinical, proof-of-principle investigation of novel therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antiparkinson Agents / therapeutic use*
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical*
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics*
  • alpha-Synuclein / genetics*


  • Antiparkinson Agents
  • alpha-Synuclein