title: Viral vector-mediated overexpression of α-synuclein as a progressive model of Parkinson's disease.
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.
authors.affiliation: Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Ayse
authors.initials: A
authors.lastname: Ulusoy
authors.forename: Mickael
authors.initials: M
authors.lastname: Decressac
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D016923:Cell Death; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D007249:Inflammation / Q000473:pathology; D016086:Lentivirus / Q000235:genetics; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D051381:Rats; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D004298:Dopamine