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Dimebon Ameliorates Amyloid-β Induced Impairments of Mitochondrial Form and Function.
MedLine Citation:
PMID:  22475801     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Due to their role in producing energy, as major sources of free radicals, and as critical regulators of apoptosis, mitochondria play a dominant role in the central nervous system (CNS). Mitochondrial dysfunction represents one major pathomechanism of Alzheimer's disease (AD), including impaired function of mitochondrial respiratory chain complexes and deficits of mitochondrial dynamics, such as impaired balance between fission and fusion mechanisms and reduced mitochondrial trafficking. Major consequences are enhanced depletion of mitochondria in axons and dendrites, synaptic dysfunction, and finally neuronal loss. Interfering with impaired mitochondrial dynamics has been proposed as novel strategy for antidementia drugs. Dimebon has been shown to improve cognition in animal models and seems to be beneficial in AD patients. Regardless of the final proof of Dimebon's clinical efficacy, it might specifically interfere with mechanisms relevant for the cognitive decline, especially by improving impaired mitochondrial function and/or dynamics in AD. Herein, we tested the effects of Dimebon on mitochondrial function and dynamics in a cellular model, overexpressing neurotoxic Aβ peptides, one of the hallmarks of AD. Dimebon exerted pronounced effects on mitochondrial morphology, respiratory chain complex activities, and enlarged mitochondrial mass. In summary, form and function of mitochondria are altered in the Aβ overexpressing cell model and precisely those changes are restored by nanomolar Dimebon treatment. Our findings support the idea that Dimebon improves mitochondrial function and that these "disease specific" effects might be relevant for interpretation and planning of future clinical trials.
Authors:
Schamim H Eckert; Janett Eckmann; Kathrin Renner-Sattler; Gunter P Eckert; Kristina Leuner; Walter E Mueller
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-4
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  -     ISSN:  1875-8908     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacology, University of Frankfurt/M, Biocenter, Frankfurt/M, Germany.
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