Mitochondria: a therapeutic target in neurodegeneration.
Mitochondrial dysfunction has long been associated with neurodegenerative disease. Therefore, mitochondrial protective agents represent a unique direction for the development of drug candidates that can modify the pathogenesis of neurodegeneration. This review discusses evidence showing that mitochondrial dysfunction has a central role in the pathogenesis of Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. We also debate the potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed antioxidants and Szeto-Schiller (SS) peptides. Since these compounds preferentially target mitochondria, a major source of oxidative damage, they are promising therapeutic candidates for neurodegenerative diseases. Furthermore, we will briefly discuss the novel action of the antihistamine drug Dimebon on mitochondria.
Moreira
Paula I
PI
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Zhu
Xiongwei
X
Wang
Xinglong
X
Lee
Hyoung-Gon
HG
Nunomura
Akihiko
A
Petersen
Robert B
RB
Perry
George
G
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism
D000975:Antioxidants; D024101:Mitochondrial Proteins