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Mitochondrial Drugs for Alzheimer Disease
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Memory and Cognition Center, University Hospitals Case Medical Center, Beachwood, OH 44122, USA
Department of Neurodegenerative Diseases, Institute of Agricultural Medicine, Lublin, Poland
UTSA Neurosciences Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249, USA
* Author to whom correspondence should be addressed.
Received: 23 October 2009; in revised form: 14 December 2009 / Accepted: 16 December 2009 / Published: 23 December 2009
Abstract: Therapeutic strategies for Alzheimer disease (AD) have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.
Keywords: Alzheimer disease; antioxidant; coenzyme Q; Dimebon; fission; fusion; mitochondria; mitochondrial drugs; mitochondrial permeability transition pore; oxidative stress
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MDPI and ACS Style
Bonda, D.J.; Wang, X.; Gustaw-Rothenberg, K.A.; Perry, G.; Smith, M.A.; Zhu, X. Mitochondrial Drugs for Alzheimer Disease. Pharmaceuticals 2009, 2, 287-298.
Bonda DJ, Wang X, Gustaw-Rothenberg KA, Perry G, Smith MA, Zhu X. Mitochondrial Drugs for Alzheimer Disease. Pharmaceuticals. 2009; 2(3):287-298.
Bonda, David J.; Wang, Xinglong; Gustaw-Rothenberg, Katarzyna A.; Perry, George; Smith, Mark A.; Zhu, Xiongwei. 2009. "Mitochondrial Drugs for Alzheimer Disease." Pharmaceuticals 2, no. 3: 287-298.