Exogenous Hsp70 exerts neuroprotective effects in peripheral nerve rupture model

Exp Neurol. 2024 Mar:373:114670. doi: 10.1016/j.expneurol.2023.114670. Epub 2023 Dec 27.

Abstract

Hsp70 is the main molecular chaperone responsible for cellular proteostasis under normal conditions and for restoring the conformation or utilization of proteins damaged by stress. Increased expression of endogenous Hsp70 or administration of exogenous Hsp70 is known to exert neuroprotective effects in models of many neurodegenerative diseases. In this study, we have investigated the effect of exogenous Hsp70 on recovery from peripheral nerve injury in a model of sciatic nerve transection in rats. It was shown that recombinant Hsp70 after being added to the conduit connecting the ends of the nerve at the site of its extended severance, migrates along the nerve into the spinal ganglion and is retained there at least three days. In animals with the addition of recombinant Hsp70 to the conduit, a decrease in apoptosis in the spinal ganglion cells after nerve rupture, an increase in the level of PTEN-induced kinase 1 (PINK1), an increase in markers of nerve tissue regeneration and a decrease in functional deficit were observed compared to control animals. The obtained data indicate the possibility of using recombinant Hsp70 preparations to accelerate the recovery of patients after neurotrauma.

Keywords: Apoptosis of neurons; Axotomy; Dorsal root ganglion; Hsp70; Neuroregeneration; Peripheral nerve injury.

MeSH terms

  • Animals
  • Apoptosis
  • Axotomy
  • Ganglia, Spinal / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / pharmacology
  • Humans
  • Nerve Regeneration
  • Neurons / metabolism
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Rats
  • Sciatic Nerve / injuries

Substances

  • Neuroprotective Agents
  • HSP70 Heat-Shock Proteins