Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification

Exp Neurol. 2017 Dec;298(Pt B):172-179. doi: 10.1016/j.expneurol.2017.07.020. Epub 2017 Jul 29.

Abstract

With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy Bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration. In applying these cutting-edge research tools with sophisticated trial designs in preclinical drug trials, a useful platform has emerged for developing candidate agents with disease modifying actions, promising a greater chance of success for clinical translation. In this article, we describe the transition of well-established animal models of PD symptomatology to newly developed models of PD pathogenesis, with specific focus on methods of viral-mediated and inoculation of pathogenic α-synuclein, that aim to aid scientific translation of neuroprotective strategies.

Keywords: Animal models; Lewy Body; Parkinson's disease; α-Synuclein.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Lewy Bodies / metabolism*
  • Lewy Bodies / pathology
  • Mutagenesis, Site-Directed / methods
  • Neurons / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein