Roadmap update: Sensory neurodegeneration in diabetes

Human diabetic polyneuropathy (DPN) is a pervasive disabling complication of both types 1 and 2 diabetes mellitus (DM). Here we build on our previous report in this journal, addressing the direct targeting of sensory neurons and the subsequent withdrawal of their distal axon terminals. Specific, albeit largely untested, translational therapeutic approaches are available to 'shore up' the sensory neuron and enable it to regrow its branches. This review provides updated information over several selected pathways our research team has been focused on. We review the evidence for sensory neuron targeting in DM including new human work, specific molecules within neuron perikarya (cell bodies) that foster sensory regeneration and newer ideas on how local nonsystemic targeting of growth cones might also promote regrowth. Our update presupposes important connections between the molecular machinery that supports intact neurons and the capacity of neurons to regrow, reversing DPN deficits. This review is limited in scope but may be a template to investigate the wide repertoire of proteins and noncoding RNAs that might be employed to eventually treat and reverse DPN.