title: Development of mitochondria-targeted aromatic-cationic peptides for neurodegenerative diseases.
abstract: 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.
authors.affiliation: Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, New York, NY 10021, USA. hhszeto@med.cornell.edu
authors.forename: Hazel H
authors.initials: HH
authors.lastname: Szeto
mesh_terms: 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
chemical_list: D002412:Cations; D010455:Peptides; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate