Expansion explosion: new clues to the pathogenesis of repeat expansion neurodegenerative diseases

The expansion in the identification of repeat expansion neurodegenerative diseases is leading to an increase in our understanding of their molecular mechanisms. Neuronal cell death is likely to be caused mainly by genetic gain-of-function mechanisms, with possible contribution from loss-of-function mechanisms as well. Postulated mechanisms involve abnormalities of protein folding, chaperone interactions, alterations in gene transcription, loss of neurotrophic support, and involvement of signal transduction pathways. Understanding the pathogenesis in these diseases is leading to the development of therapeutic strategies.