Abstract
Alzheimers is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. The progressive and multifaceted degenerative phenotype of Alzheimers suggests that successful treatment strategies necessarily will be equally multi-faceted and disease stage specific. Traditional therapeutic strategies based on the pathological aspect of the disease have achieved success in preclinical models which has not translated into clinical therapeutic efficacy. Meanwhile, increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. The essential role of mitochondrial bioenergetics and the unique trajectory of alterations in brain metabolic capacity enable a bioenergetic- centric strategy that targets disease-stage specific pattern of brain metabolism for disease prevention and treatment. A combination of nutraceutical and pharmaceutical intervention that enhances glucose-driven metabolic activity and potentiates mitochondrial bioenergetic function could prevent the antecedent decline in brain glucose metabolism, promote healthy aging and prevent AD. Alternatively, during the prodromal incipient phase of AD, sustained activation of ketogenic metabolic pathways coupled with supplement of the alternative fuel source, ketone bodies, could sustain mitochondrial bioenergetic function to prevent or delay further progression of the disease.
Keywords: Mitochondria, Bioenergetics, Alzheimer's disease, Ketogenesis, Hypometabolism, Oxidative Stress, aging, Krebs cycle, curcumin, vitamin E
Current Pharmaceutical Design
Title: Targeting Mitochondrial Bioenergetics for Alzheimers Prevention and Treatment
Volume: 17 Issue: 31
Author(s): Jia Yao and Roberta Diaz Brinton
Affiliation:
Keywords: Mitochondria, Bioenergetics, Alzheimer's disease, Ketogenesis, Hypometabolism, Oxidative Stress, aging, Krebs cycle, curcumin, vitamin E
Abstract: Alzheimers is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. The progressive and multifaceted degenerative phenotype of Alzheimers suggests that successful treatment strategies necessarily will be equally multi-faceted and disease stage specific. Traditional therapeutic strategies based on the pathological aspect of the disease have achieved success in preclinical models which has not translated into clinical therapeutic efficacy. Meanwhile, increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. The essential role of mitochondrial bioenergetics and the unique trajectory of alterations in brain metabolic capacity enable a bioenergetic- centric strategy that targets disease-stage specific pattern of brain metabolism for disease prevention and treatment. A combination of nutraceutical and pharmaceutical intervention that enhances glucose-driven metabolic activity and potentiates mitochondrial bioenergetic function could prevent the antecedent decline in brain glucose metabolism, promote healthy aging and prevent AD. Alternatively, during the prodromal incipient phase of AD, sustained activation of ketogenic metabolic pathways coupled with supplement of the alternative fuel source, ketone bodies, could sustain mitochondrial bioenergetic function to prevent or delay further progression of the disease.
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Cite this article as:
Yao Jia and Diaz Brinton Roberta, Targeting Mitochondrial Bioenergetics for Alzheimers Prevention and Treatment, Current Pharmaceutical Design 2011; 17 (31) . https://dx.doi.org/10.2174/138161211798072517
DOI https://dx.doi.org/10.2174/138161211798072517 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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