Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease
Stockburger C, Eckert S, Eckert GP, Friedland K, Mueller WE (2018)
Publication Type: Book chapter / Article in edited volumes
Publication year: 2018
Edited Volumes: Volume 6: Alzheimer's Disease: New Beginnings
Series: Advances in Alzheimer's Disease
Book Volume: 6
Pages Range: 453-465
ISBN: 978-1-61499-875-4
DOI: 10.3233/978-1-61499-876-1-453
Abstract
Because of the failure of all amyloid-beta directed treatment strategies for Alzheimer's disease (AD), the concept of mitochondrial dysfunction as a major pathomechanism of the cognitive decline in aging and AD has received substantial support. Accordingly, improving mitochondrial function as an alternative strategy for new drug development became of increasing interest and many different compounds have been identified which improve mitochondrial function in preclinical in vitro and in vivo experiments. However, very fewif any have been investigated in clinical trials, representing a major drawback of the mitochondria directed drug development. To overcome these problems, we used a top-down approach by investigating several older antidementia drugs with clinical evidence of therapeutic efficacy. These include EGb761 (R) (standardized ginkgo biloba extract), piracetam, and Dimebon. All improve experimentally many aspects of mitochondrial dysfunction including mitochondrial dynamics and also improve cognition and impaired neuronal plasticity, the functionally most relevant consequences of mitochondrial dysfunction. All partially inhibit opening events of the mitochondrial permeability transition pore (mPTP) which previously has mainly been discussed as a mechanism relevant for the induction of apoptosis. However, as more recent work suggests the mPTP as a master regulator of many mitochondrial functions, our data suggest the mPTP as a possible relevant drug target within the love triangle between mPTP regulation, mitochondrial dynamics, and mitochondrial function including regulation of neuronal plasticity. Drugs interfering with mPTP function will improve not only mitochondrial impairment in aging and AD but also will have beneficial effects on impaired neuronal plasticity, the pathomechanism which correlates best with functional deficits (cognition, behavior) in aging and AD.
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Germany (DE)How to cite
APA:
Stockburger, C., Eckert, S., Eckert, G.P., Friedland, K., & Mueller, W.E. (2018). Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease. In George Perry, Jesús Avila, Paula I. Moreira, Aaron A. Sorensen, Massimo Tabaton (Eds.), Volume 6: Alzheimer's Disease: New Beginnings. (pp. 453-465).
MLA:
Stockburger, Carola, et al. "Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease." Volume 6: Alzheimer's Disease: New Beginnings. Ed. George Perry, Jesús Avila, Paula I. Moreira, Aaron A. Sorensen, Massimo Tabaton, 2018. 453-465.
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