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

• Published in: Neurobiology of disease 2019-01, Vol.121, p.17-33
• Main Authors: MacDougall, Gabriella, Anderton, Ryan S., Mastaglia, Frank L., Knuckey, Neville W., Meloni, Bruno P.
• Format: Article
• Language: English
• Subjects: Apoptosis; Cationic arginine-rich peptides; Ischaemia; Membrane potential; Mito-protection; Mitochondria; Oxidative stress; Permeability transition; Stroke
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2018.09.010

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. •There are currently no clinically effective neuroprotective therapeutics available for stroke patients.•Mitochondria are a critical central mediator in determining the fate of neuronal and glial cells during stroke.•CARPs are novel neuroprotective agents that have exhibited potent neuroprotection by targeting mitochondria during stroke.•Mitoprotection is a new avenue of targeted drug development and may translate to better clinical outcomes in stroke trials.