An Wu, Xueyi Li
Huntington's disease (HD) is a life-threatening neurodegenerative disease caused by a mutation in Huntingtin (HTT). Neuropathology in HD is marked by a progressive loss of neurons in the caudate putamen and the deposition of mutant HTT aggregates as cytoplasmic and nuclear inclusions. At present, no disease-modifying treatment for HD exists. Vesicular trafficking is a fundamental way to target proteins to their functional sites and thus essential for the maintenance of cellular homeostasis. HTT associates with vesicles and interacts with molecular motor proteins driving vesicle movement along cytoskeletons and with the molecular machines orchestrating vesicle formation, tethering and fusion. Rab proteins play key roles in each of the four major steps in vesicular trafficking. Here we provide an overview of Rab proteins perturbed in HD, how their disturbance contributes to disease progression, and ways to target them for therapy in Huntington's disease (HD).