A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice

Int J Mol Sci. 2021 May 2;22(9):4829. doi: 10.3390/ijms22094829.

Abstract

It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1's EGF3 domain (residues 407-422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH.

Keywords: Netrin-1; hemin; intracerebral hemorrhage; neuroprotection; peptide.

MeSH terms

  • Animals
  • Apoptosis
  • Behavior, Animal
  • Cell Death / drug effects*
  • Cell Survival
  • Cerebral Hemorrhage / drug therapy*
  • DCC Receptor / genetics
  • Disease Models, Animal
  • Focal Adhesion Protein-Tyrosine Kinases
  • HEK293 Cells
  • Humans
  • Mice
  • Netrin-1 / genetics
  • Netrin-1 / metabolism*
  • Netrin-1 / pharmacology*
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / pharmacology*

Substances

  • DCC Receptor
  • Dcc protein, mouse
  • Neuroprotective Agents
  • Ntn1 protein, mouse
  • Netrin-1
  • Focal Adhesion Protein-Tyrosine Kinases