Autophagy-targeting modulation to promote peripheral nerve regeneration

Abstract

Abstract Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms. Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration. However, recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration, particularly in the context of traumatic injuries. Consequently, autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration. Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths, thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation. These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration. A range of autophagy- inducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries. This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration, summarizing the potential drugs and interventions that can be harnessed to promote this process. We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.