Viral vectors, animal models and new therapies for Parkinson's disease.
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.
Schneider
Bernard
B
Laboratory for the Study of Neurodegeneration, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH-1015 Lausanne, Switzerland.
Zufferey
Romain
R
Aebischer
Patrick
P
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
D051844:alpha-Synuclein