Pathways to motor incoordination: The inherited ataxias

Two groups of hereditary ataxias are most relevant to humans-the autosomal recessive ataxias and the autosomal dominant spinocerebellar ataxias. Recessive ataxias are multisystem disorders that are characterized by inactivating mutations that result in loss of protein function. By contrast, cell death associated with dominant spinocerebellar ataxias is mostly restricted to the CNS, and cellular control of protein folding and processing is affected. The purpose of this review is to provide an integrated view of the field, encompassing the similarities-which are few-and the differences-which are many-between pathological processes that cause ataxia. In reviewing the current knowledge of ataxias, we discuss recent insights into the pathogenic mechanisms that lead to specific neuronal dysfunction and neurodegeneration.