Mitochondria-targeted peptide antioxidants: novel neuroprotective agents.
Increasing evidence suggests that mitochondrial dysfunction and oxidative stress play a crucial role in the majority of neurodegenerative diseases. Mitochondria are a major source of intracellular reactive oxygen species (ROS) and are particularly vulnerable to oxidative stress. Oxidative damage to mitochondria has been shown to impair mitochondrial function and lead to cell death via apoptosis and necrosis. Because dysfunctional mitochondria will produce more ROS, a feed-forward loop is set up whereby ROS-mediated oxidative damage to mitochondria favors more ROS generation, resulting in a vicious cycle. It is now appreciated that reduction of mitochondrial oxidative stress may prevent or slow down the progression of these neurodegenerative disorders. However, if mitochondria are the major source of intracellular ROS and mitochondria are most vulnerable to oxidative damage, then it would be ideal to deliver the antioxidant therapy to mitochondria. This review will summarize the development of a novel class of mitochondria-targeted antioxidants that can protect mitochondria against oxidative stress and prevent neuronal cell death in animal models of stroke, Parkinson's disease, and amyotrophic lateral sclerosis.
Szeto
Hazel H
HH
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. hhszeto@med.cornell.edu
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species