Viral vectors, animal models and new therapies for Parkinson’s disease.
July 3rd, 2008 | by admin |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 B, Zufferey R, Aebischer P.
Laboratory for the Study of Neurodegeneration, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 15, CH-1015 Lausanne, Switzerland.