Traffic signaling: new functions of huntingtin and axonal transport in neurological disease

Over the past twenty years there have been numerous advances in our understanding of Huntington's disease (HD) and other neurodegenerative proteopathies such as Alzheimer's disease and Parkinson's disease. In each case, disease-specific proteins are expressed and accumulate; what has been less clear is precisely what problems are caused by the accumulation. Recently we have begun to appreciate that increased protein levels or changes in the ratios of different isoforms affect the movement of molecules along the axon, thereby disrupting neuronal function. Huntingtin, the protein involved in HD, plays a special role in axonal transport, and very recent studies have found that its activity - and the movement of its cargoes - is altered not only in HD but in other neurological diseases. Here, we contextualize these studies and consider how modulating huntingtin activity could provide new avenues to therapy.