TY - JOUR
T1 - Mitochondria and neuroprotection in stroke
T2 - Cationic arginine-rich peptides (CARPs) as a novel class of mitochondria-targeted neuroprotective therapeutics
AU - MacDougall, Gabriella
AU - Anderton, Ryan S.
AU - Mastaglia, Frank L.
AU - Knuckey, Neville W.
AU - Meloni, Bruno P.
PY - 2019/1
Y1 - 2019/1
N2 - 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 mitochondria] dysfunction in ischaemic stroke pathophysiology and highlights the potential beneficial effects of CARPs on mitochondria in the ischaemic brain following stroke.
AB - 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 mitochondria] dysfunction in ischaemic stroke pathophysiology and highlights the potential beneficial effects of CARPs on mitochondria in the ischaemic brain following stroke.
KW - Stroke
KW - Ischaemia
KW - Cationic arginine-rich peptides
KW - Mitochondria
KW - Mito-protection
KW - Oxidative stress
KW - Membrane potential
KW - Permeability transition
KW - Apoptosis
KW - CELL-PENETRATING PEPTIDES
KW - ISCHEMIC BRAIN-INJURY
KW - FOCAL CEREBRAL-ISCHEMIA
KW - PROTECTS HIPPOCAMPAL-NEURONS
KW - PERMEABILITY TRANSITION PORE
KW - SUBSEQUENT DNA FRAGMENTATION
KW - APOPTOSIS-INDUCING FACTOR
KW - AP-1 INHIBITORY PEPTIDES
KW - NA-1 TAT-NR2B9C PEPTIDES
KW - NITRIC-OXIDE SYNTHASE
U2 - 10.1016/j.nbd.2018.09.010
DO - 10.1016/j.nbd.2018.09.010
M3 - Review article
C2 - 30218759
VL - 121
SP - 17
EP - 33
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -