Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases.

Autor: Chaturvedi RK; Developmental Toxicology Division, Systems Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 80 MG Marg, Lucknow 226001, India. rajnish@iitr.res.in, Beal MF
Jazyk: angličtina
Zdroj: Molecular and cellular neurosciences [Mol Cell Neurosci] 2013 Jul; Vol. 55, pp. 101-14. Date of Electronic Publication: 2012 Dec 05.
DOI: 10.1016/j.mcn.2012.11.011
Abstrakt: Substantial evidence from both genetic and toxin induced animal and cellular models and postmortem human brain tissue indicates that mitochondrial dysfunction plays a central role in pathophysiology of the neurodegenerative disorders including Parkinson's disease (PD), and Huntington's disease (HD). This review discusses the emerging understanding of the role of mitochondrial dysfunction including bioenergetics defects, mitochondrial DNA mutations, familial nuclear DNA mutations, altered mitochondrial fusion/fission and morphology, mitochondrial transport/trafficking, altered transcription and increased interaction of pathogenic proteins with mitochondria in the pathogenesis of PD and HD. This review recapitulates some of the key therapeutic strategies applied to surmount mitochondrial dysfunction in these debilitating disorders. We discuss the therapeutic role of mitochondrial bioenergetic agents such as creatine, Coenzyme-Q10, mitochondrial targeted antioxidants and peptides, the SIRT1 activator resveratrol, and the pan-PPAR agonist bezafibrate in toxin and genetic cellular and animal models of PD and HD. We also summarize the phase II-III clinical trials conducted using some of these agents. Lastly, we discuss PGC-1α, TORC and Sirtuins as potential therapeutic targets for mitochondrial dysfunction in neurodegenerative disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.
(Copyright © 2012 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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