Induction of Autophagy and Its Role in Peripheral Nerve Regeneration after Peripheral Nerve Injury

Int J Mol Sci. 2023 Nov 11;24(22):16219. doi: 10.3390/ijms242216219.


No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.

Keywords: autophagy; degeneration; facial nerve; regeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy
  • Melatonin* / metabolism
  • Mice
  • Nerve Regeneration
  • Peripheral Nerve Injuries* / metabolism
  • Peripheral Nerves
  • Prospective Studies
  • Rats
  • Retrospective Studies
  • Sciatic Nerve / metabolism


  • Melatonin

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF 2018R1A6A1A03025124) (NRF 2019R1A2C1086807) (NRF 2022R1A2C1091779). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HV22C0233). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.