Viral vector-mediated overexpression of α-synuclein as a progressive model of Parkinson's disease

Prog Brain Res. 2010;184:89-111. doi: 10.1016/S0079-6123(10)84005-1.

Abstract

The discovery of the role of α-synuclein in the pathogenesis of Parkinson's disease (PD) has opened new possibilities for the development of more authentic models of Parkinson's disease. Recombinant adeno-associated virus (AAV) and lentivirus (LV) vectors are efficient tools for expression of genes locally in subsets of neurons in the brain and can be used to express human wild-type or mutated α-synuclein selectively in midbrain dopamine neurons. Using this approach, it is possible to trigger extensive PD-like cellular and axonal pathologies in the nigrostriatal projection, involving abnormal protein aggregation, neuronal dysfunction, and cell death that develop progressively over time. Targeted overexpression of human α-synuclein in midbrain dopamine neurons, using AAV vectors, reproduces many of the characteristic features of the human disease and provides, for the first time, a model of progressive PD that can be applied to both rodents and primates.

Publication types

  • Review

MeSH terms

  • Animals
  • Axons / pathology
  • Cell Death
  • Dependovirus / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Dopamine / biosynthesis
  • Dopamine / metabolism
  • Dopamine / physiology
  • Genetic Vectors
  • Humans
  • Inflammation / pathology
  • Lentivirus / genetics
  • Neurons / pathology
  • Parkinson Disease / genetics*
  • Parkinson Disease / immunology
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Protein Processing, Post-Translational
  • Rats
  • alpha-Synuclein / biosynthesis
  • alpha-Synuclein / genetics*

Substances

  • alpha-Synuclein
  • Dopamine