Ion channel dysfunction in cerebellar ataxia

摘要

Cerebellar ataxias constitute a heterogeneous group of disorders that result in impaired speech, uncoordinated limb movements, and impaired balance, often ultimately resulting in wheelchair confinement. Motor dysfunction in ataxia can be attributed to dysfunction and degeneration of neurons in the cerebellum and its associated pathways. Recent work has suggested the importance of cerebellar neuronal dysfunction resulting from mutations in specific ion-channels that regulate membrane excitability in the pathogenesis of cerebellar ataxia in humans. Importantly, even in ataxias not directly due to ion-channel mutations, transcriptional changes resulting in ion-channel dysfunction are tied to motor dysfunction and degeneration in models of disease. In this review, we describe the role that ion-channel dysfunction plays in a variety of cerebellar ataxias, and postulate that a potential therapeutic strategy that targets specific ion-channels exists for cerebellar ataxia.