title: Viral vectors, animal models and new therapies for Parkinson's disease.
abstract: The involvement of alpha-synuclein in familial forms of Parkinson's disease suggests a potential causative role in the pathogenesis. We have explored the possibility of generating animal models of Parkinson's disease by overexpressing alpha-synuclein in the nigrostriatal pathway using viral vectors. Both lentiviral and adeno-associated vectors efficiently transduce dopaminergic neurons in the substantia nigra, and transgenic expression of alpha-synuclein leads to the progressive loss of neurons positive for dopaminergic markers, with the formation of intraneuronal alpha-synuclein aggregates. With a high tropism for nigral dopaminergic neurons, adeno-associated vectors allow for the monitoring of dopaminergic function using spontaneous and drug-induced behaviour. We propose that virus-based rodent alpha-synuclein models provide a valuable approach for the preclinical testing of therapeutics.
authors.affiliation: Laboratory for the Study of Neurodegeneration, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH-1015 Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Schneider
authors.forename: Romain
authors.initials: R
authors.lastname: Zufferey
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000502:physiology*; D010300:Parkinson Disease / Q000628:therapy*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein