Role of HspB1 and HspB8 in hereditary peripheral neuropathies: beyond the chaperone function

Within the last ten years, mutations in genes encoding the small heat shock proteins (also called HspB) HspB1, HspB4, HspB5 and HspB8 have been associated with neurological and muscular disorders. In particular, HspB1 and HspB8 mutations result in hereditary peripheral neuropathies, which primarily affect motor and/or sensory peripheral neurons. Due to their extremely long axons, peripheral neurons are particularly dependent on an efficient vesicular trafficking and axonal transport, whose defects have been directly linked to the development of hereditary peripheral neuropathies. Genetic analyses generated new insights into the molecular pathways involved in hereditary peripheral neuropathies, which include not only vesicular trafficking but also protein quality control, protein degradation and RNA processing. This review summarizes the current understanding of HspB implication in motor diseases, starting with a general picture of HspB functions followed by a description of new emerging roles for HspB1 and HspB8 in axonal transport, protein sorting and degradation.