Molecular mechanism underlying axonal degeneration and possible therapeutic mechanisms to promote regeneration

Neuronal degeneration can result in many of destructive diseases such as Alzheimer’s disease, ALS, ataxia, Parkinson’s disease and muscular atrophy. With much of the research in neuroscience dedicated to addressing the underlying mechanisms of axonal degeneration, there still remains a vast amount of unknown to be explicated. There are three distinct pathways in which the axon undergoes degeneration: cell apoptosis, axon pruning and Wallerian degeneration. Each of these routes involve unique initiation signals as well as the key players involved in facilitating degeneration. Recent progress has identified number of molecular effectors demonstrating its notable function in neuronal degeneration such as NMNAT, SIRT1 and Sarm1. The ultimate goal in further understanding these mechanisms is to achieve clinically translational therapy to prevent or recover from neuron degeneration. In contrast to PNS regeneration, which can be acquired to a significant level, CNS is notorious for resisting instinctive regeneration. Number of intrinsic inhibitory signals such as low production of neurotrophins and regeneration associated genes as well as extrinsic inhibitory signals such as glial scars and myelin associated inhibitors have been identifies so far. Through further research in elucidating the difference between PNS and CNS regeneration cues will guide in creating a more encouraging environment for CNS regeneration to cure diseases caused by CNS neuronal loss.