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

By Ayse Ulusoy, Mickael Decressac, Deniz Kirik and Anders Björklund


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

Topics: Neurosciences, Synuclein, Dopamine, Nigrostriatal system, Motor impairment, Adeno-associated virus, Lentivirus, Viral vectors, Animal models
Publisher: 'Elsevier BV'
Year: 2010
DOI identifier: 10.1016/S0079-6123(10)84005-1
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