Insights from mouse models into the molecular basis of neurodegeneration

Thanks largely to cloning the genes for several neurodegenerative diseases over the past decade and the existence of mouse mutants, the molecular basi s of neurodegeneration is finally beginning to yield some of its secrets. W e discuss what has been learned about the pathogenesis of "triplet repeat" diseases through mouse models for spinocerebellar ataxia types 1 and 3 and Huntington disease, including the roles of nuclear aggregates and protein c leavage. We also discuss the neurologic phenotypes that arise from mutation s in neurotransmitter receptors (lurcher mice) and ion channels (weaver, le aner; and tottering mice), drawing parallels between ischemic cell death an d the neurodegeneration that occurs in the lurcher mouse. Finally, we discu ss common mechanisms of cell death and lessons learned from these mouse mod els that might have broader relevance to other neurologic disorders.