Parkinson's disease (PD) is characterized by the progressive loss of substantia 
nigra dopaminergic neurons and the presence of cytoplasmic inclusions named Lewy 
bodies. Two missense mutations of the alpha-synuclein (alpha-syn; A30P and A53T) 
have been described in several families with an autosomal dominant form of PD. 
alpha-Syn also constitutes one of the main components of Lewy bodies in sporadic 
cases of PD. To develop an animal model of PD, lentiviral vectors expressing 
different human or rat forms of alpha-syn were injected into the substantia 
nigra of rats. In contrast to transgenic mice models, a selective loss of nigral 
dopaminergic neurons associated with a dopaminergic denervation of the striatum 
was observed in animals expressing either wild-type or mutant forms of human 
alpha-syn. This neuronal degeneration correlates with the appearance of abundant 
alpha-syn-positive inclusions and extensive neuritic pathology detected with 
both alpha-syn and silver staining. Lentiviral-mediated expression of wild-type 
or mutated forms of human alpha-syn recapitulates the essential 
neuropathological features of PD. Rat alpha-syn similarly leads to protein 
aggregation but without cell loss, suggesting that inclusions are not the 
primary cause of cell degeneration in PD. Viral-mediated genetic models may 
contribute to elucidate the mechanism of alpha-syn-induced cell death and allow 
the screening of candidate therapeutic molecules.