Targeting mitochondrial bioenergetics for Alzheimer's prevention and treatment.

TitleTargeting mitochondrial bioenergetics for Alzheimer's prevention and treatment.
Publication TypeJournal Article
Year of Publication2011
AuthorsYao J, Brinton RDiaz
JournalCurr Pharm Des
Date Published2011
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Central Nervous System Agents, Humans, Mitochondria, Molecular Targeted Therapy, Oxidative Stress

Alzheimer's 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 Alzheimer's 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.

Alternate JournalCurr. Pharm. Des.
PubMed ID21902662
PubMed Central IDPMC4209948
Grant ListR01 AG032236 / AG / NIA NIH HHS / United States
2R01AG032236 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D