Autophagy's Role in Facial Nerve Regeneration: A Comprehensive Review

The facial nerve is highly susceptible to injury within the maxillofacial region. Recent studies have demonstrated that autophagy, which involves lysosomal degradation of synaptic components, occurs within hours of facial nerve transection [135]. Schwann cells, the primary glia in the peripheral nervous system, play a crucial role in facilitating axon regeneration after nerve injury [136]. Research has confirmed that autophagy is involved in regulating Schwann cell function after peripheral nerve injury [137]. In fact, a recent study showed that CXCL12 can promote Schwann cell migration and increase autophagy, leading to improved nerve regeneration [138]. Conversely, inhibiting autophagy by 3-MA or ATG7 gene knockout can hinder nerve fiber disintegration, weaken Schwann cell accumulation, and delay tissue debris removal and nerve regeneration [139, 140]. Mice with normal autophagy function have better axon regeneration and myelination than those with inhibited autophagy [139, 140]. Furthermore, promoting autophagy using a 3D melatonin-controlled release scaffold can increase nerve proliferation, reduce Schwann cell apoptosis, and facilitate debris clearance, providing a favorable environment for nerve engineering [141]. In another study, overexpressing X-box protein 1 (XBP1) to promote autophagy facilitated nerve axon regeneration and motor function recovery [142]. Exogenous nerve growth factor administration also activated autophagy in dedifferentiated Schwann cells, promoting myelin debris clearance and axon and myelin regeneration after peripheral nerve injury [143]. Finally, chorda tympani denervation in rats activated autophagy and lysosomal proteolytic systems in the submandibular gland, leading to aquaporin5 degradation and subsequent salivary gland resting secretion increase [144].