期刊
PARKINSONISM & RELATED DISORDERS
卷 15, 期 -, 页码 S189-S194出版社
ELSEVIER SCI LTD
DOI: 10.1016/S1353-8020(09)70812-0
关键词
Creatine; Coenzyme Q10; Triterpenoids; Antioxidant response element; Oxidative stress; Mitochondrial biogenesis; PGC-1 alpha
资金
- Department of Defense
- NIH
- Parkinson's Disease Foundation
A large body of evidence from postmortem brain tissue and genetic analysis in humans, as well as biochemical and pathological studies in animal models of neurodegeneration suggest that mitochondrial dysfunction is a key pathological mechanism in Parkinson's Disease (PD). Mitochondrial dysfunction leads to oxidative stress, damage to mitochondrial DNA, mitochondrial DNA deletions, altered mitochondrial morphology, alterations in mitochondrial fission and fusion and ultimately neuronal demise. Therapeutic approaches targeting mitochondrial dysfunction and oxidative damage, therefore, hold great promise in PD. A number of agents, which target energy metabolism, are presently in therapeutic trials in PD. Both creatine and Coenzyme Q10 (CoQ10) are being tested in phase III clinical trials. In addition, preclinical studies in animal models have shown efficacy of mitochondrial-targeted antioxidants and the SS peptides. A promising approach for increasing antioxidant defenses is to transcriptionally increase the activity of the Nrf2/ARE pathway, which activates transcription of anti-inflammatory and antioxidant genes. A number of agents including sulforaphane, curcumin and triterpenoids have been shown to activate this pathway and to produce neuroprotective effects. Lastly, newly identified therapeutic targets include peroxisomal proliferator activated receptor gamma-coactivator (PGC-1alpha) and sirtuins. These pathways provide promise for future therapeutic developments in the treatment of PD. (C) 2009 Elsevier Ltd. All rights reserved.
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