Development of mitochondria-targeted aromatic-cationic peptides for neurodegenerative diseases.
Mitochondrial impairment and oxidative damage are intimately involved in the pathogenesis of neurodegenerative diseases. Which is the initiating event is probably irrelevant because each can set into motion a self-sustaining and amplifying feed-forward cycle between reactive oxygen species (ROS) generation and mitochondrial impairment. Recent approaches to the development of neuroprotective agents have therefore targeted mitochondria protection and/or reduction of oxidative stress. There are several hurdles in the quest for neuroprotective drugs. The difficulties include penetration of the blood-brain barrier and delivery of drugs to mitochondria. Here we describe a novel class of mitochondria-targeted peptides that can promote mitochondrial function, reduce mitochondrial ROS generation, inhibit mitochondrial permeability transition, and prevent apoptosis and necrosis. These peptides can readily penetrate the blood-brain barrier and have demonstrated efficacy in animal models of Parkinson's disease and amyotrophic lateral sclerosis.
Szeto
Hazel H
HH
Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, New York, NY 10021, USA. hhszeto@med.cornell.edu
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002412:Cations; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D023421:Models, Animal; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018384:Oxidative Stress; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
D002412:Cations; D010455:Peptides; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate