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

Research output: Contribution to journalReview article

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.

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Authors
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Synuclein, Dopamine, Nigrostriatal system, Motor impairment, Adeno-associated virus, Lentivirus, Viral vectors, Animal models
Original languageEnglish
Pages (from-to)89-111
Number of pages23
JournalProgress in Brain Research
Volume184
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes