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Mitochondrial Approaches for Neuroprotection
Author(s) -
Chaturvedi Rajnish K.,
Beal M. Flint
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.1427.027
Subject(s) - coenzyme q10 , neurodegeneration , neuroprotection , amyotrophic lateral sclerosis , mitochondrion , biology , oxidative stress , mitochondrial disease , mitochondrial dna , idebenone , pharmacology , medicine , bioinformatics , neuroscience , disease , pathology , genetics , biochemistry , gene
A large body of evidence from postmortem brain tissue and genetic analysis in humans and biochemical and pathological studies in animal models (transgenic and toxin) of neurodegeneration suggest that mitochondrial dysfunction is a common pathological mechanism. Mitochondrial dysfunction from oxidative stress, mitochondrial DNA deletions, pathological mutations, altered mitochondrial morphology, and interaction of pathogenic proteins with mitochondria leads to neuronal demise. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. This review discusses the potential therapeutic efficacy of creatine, coenzyme Q10, idebenone, synthetic triterpenoids, and mitochondrial targeted antioxidants (MitoQ) and peptides (SS‐31) in in vitro studies and in animal models of Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We have also reviewed the current status of clinical trials of creatine, coenzyme Q10, idebenone, and MitoQ in neurodegenerative disorders. Further, we discuss newly identified therapeutic targets, including peroxisome proliferator‐activated receptor‐γ‐coactivator and sirtuins, which provide promise for future therapeutic developments in neurodegenerative disorders.