ATP synthase and Alzheimer's disease: putting a spin on the mitochondrial hypothesis

Ebanks, Brad; Ingram, Thomas L.; Chakrabarti, Lisa

Abstract

It is estimated that over 44 million people across the globe have dementia, and half of these cases are believed to be Alzheimer's disease (AD). As the proportion of the global population which is over the age 60 increases so will the number of individuals living with AD. This will result in ever-increasing demands on healthcare systems and the economy. AD can be either sporadic or familial, but both present with similar pathobiology and symptoms. Three prominent theories about the cause of AD are the amyloid, tau and mitochondrial hypotheses. The mitochondrial hypothesis focuses on mitochondrial dysfunction in AD, however little attention has been given to the potential dysfunction of the mitochondrial ATP synthase in AD. ATP synthase is a proton pump which harnesses the chemical potential energy of the proton gradient across the inner mitochondrial membrane (IMM), generated by the electron transport chain (ETC), in order to produce the cellular energy currency ATP. This review presents the evidence accumulated so far that demonstrates dysfunction of ATP synthase in AD, before highlighting two potential pharmacological interventions which may modulate ATP synthase.

Citation

Ebanks, B., Ingram, T. L., & Chakrabarti, L. (2020). ATP synthase and Alzheimer's disease: putting a spin on the mitochondrial hypothesis. Aging, 12(6), 16647—16662. https://doi.org/10.18632/aging.103867

• Journal Article Type: Article
• Acceptance Date: Jul 21, 2020
• Online Publication Date: Aug 27, 2020
• Publication Date: Aug 31, 2020
• Deposit Date: Aug 6, 2020
• Publicly Available Date: Sep 27, 2022
• Journal: Aging
• Electronic ISSN: 1945-4589
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 6
• Pages: 16647—16662
• DOI: https://doi.org/10.18632/aging.103867
• Public URL: https://nottingham-repository.worktribe.com/output/4814666
• Publisher URL: https://www.aging-us.com/article/103867/text