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Development of Mitochondria‐targeted Aromatic‐cationic Peptides for Neurodegenerative Diseases
Author(s) -
Szeto Hazel H.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1427.013
Subject(s) - mitochondrion , cationic polymerization , chemistry , neuroscience , biochemistry , microbiology and biotechnology , biology , organic chemistry
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.