Advances in genetic models of Parkinson's disease

Parkinson's disease (PD) is the second most common neurological cause of death, after Alzheimer's disease, in elderly people. PD is characterized by a variety of motoric dysfunctions resulting from the loss of striatal dopamine, which accompany progressive degeneration of dopaminergic neurons in the substantia nigra. While the causes of PD remain elusive in most cases, recent molecular genetic studies have linked mutations in the alpha-synuclein gene with a rare form of familial PD and mutations in the parkins gene with an autosomal recessive form of familial PD. Identification of these genes is allowing for creation of genetic models where in vivo degenerative processes can be studied. In particular, various transgenic animals expressing human alpha-synuclein variants have demonstrated that alpha-synuclein abnormalities can lead to neurodegenerative changes in vivo. These and other genetic models of nigrostriatal degeneration will allow investigators to define in vivo cellular mechanisms that are relevant to PD pathogenesis. (C) 2001 Elsevier Science B.V. All rights reserved.