Valproic Acid: A Potential Therapeutic for Spinal Cord Injury

Cell Mol Neurobiol. 2021 Oct;41(7):1441-1452. doi: 10.1007/s10571-020-00929-9. Epub 2020 Jul 28.

Abstract

The lack of an effective pharmaceutical agent for spinal cord injury (SCI) is a current problematic situation for clinicians, as the rate of motor vehicle accidents among young adults is on the rise. SCI contributes to the high disability rate. Presently, evidences detailing the precise pathological mechanisms in SCI are limited, compounding to the unavailability of an effective treatment method. Surgery, though not a complete curative method, is useful in managing some of the associated symptoms of secondary SCI. Autophagy and inflammation are contributive factors to both exacerbation and improvement of SCI. The mammalian target of rapamycin (mTOR) signaling pathway is a key player in the regulation of inflammatory response and autophagy. Valproic acid (VPA), a clinically used antiepileptic drug, has been suggested to improve neurological conditions, including SCI. This report reviewed the correlation between mTOR and autophagy, as well as autophagy's role and the therapeutic effects of VPA in SCI. VPA regulates autophagy by potentially inhibiting mTORC1, a complex of mTOR, while also hindering inflammatory response. Conclusively, an effective treatment for SCI could lie in the timely regulation of mTOR signaling pathway, and VPA could be the potential drug that improves SCI owing to its propensity to regulate the mTOR signaling pathway.

Keywords: Autophagy; Inflammation; Spinal cord injury; Valproic acid; mTOR signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Recovery of Function / drug effects*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • TOR Serine-Threonine Kinases / drug effects*
  • TOR Serine-Threonine Kinases / metabolism
  • Valproic Acid / metabolism
  • Valproic Acid / pharmacology*

Substances

  • Valproic Acid
  • TOR Serine-Threonine Kinases