Mitochondria: A Therapeutic Target in Neurodegeneration

Paula I. Moreira (1) , Xiongwei Zhu (2) , Xinglong Wang (2) , Hyoung-Gon Lee (2) , Akihiko Nunomura (3) , Robert B. Petersen (2) , George Perry (2, 4) , Mark A. Smith (2)

1 University of Coimbra
2 Department of Pathology
3 Department of Neuropsychiatry
4 UTSA - The University of Texas at San Antonio

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.

Mots clés: metabolic antioxidants; mitochondria; mitochondria-directed antioxidants; neurodegeneration; SS peptides

Paula I. Moreira, Xiongwei Zhu, Xinglong Wang, Hyoung-Gon Lee, Akihiko Nunomura, et al.. Mitochondria: A Therapeutic Target in Neurodegeneration. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1802 (1), pp.212. ⟨10.1016/j.bbadis.2009.10.007⟩. ⟨hal-00562943⟩