Mitochondria and neuroprotection in stroke: Cationic arginine-rich peptides (CARPs) as a novel class of mitochondria-targeted neuroprotective therapeutics

Neurobiol Dis. 2019 Jan:121:17-33. doi: 10.1016/j.nbd.2018.09.010. Epub 2018 Sep 13.

Abstract

Stroke is the second leading cause of death globally and represents a major cause of devastating long-term disability. Despite sustained efforts to develop clinically effective neuroprotective therapies, presently there is no clinically available neuroprotective agent for stroke. As a central mediator of neurodamaging events in stroke, mitochondria are recognised as a critical neuroprotective target, and as such, provide a focus for developing mitochondrial-targeted therapeutics. In recent years, cationic arginine-rich peptides (CARPs) have been identified as a novel class of neuroprotective agent with several demonstrated mechanisms of action, including their ability to target mitochondria and exert positive effects on the organelle. This review provides an overview on neuronal mitochondrial dysfunction in ischaemic stroke pathophysiology and highlights the potential beneficial effects of CARPs on mitochondria in the ischaemic brain following stroke.

Keywords: Apoptosis; Cationic arginine-rich peptides; Ischaemia; Membrane potential; Mito-protection; Mitochondria; Oxidative stress; Permeability transition; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arginine / administration & dosage*
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Peptides / administration & dosage*
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Peptides
  • Arginine