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Mechanisms of Mitochondrial Dysfunction in Alzheimer’s Disease

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Abstract

Mitochondria are the primary source for energy generation in the cell, which manifests itself in the form of the adenosine triphosphate (ATP). Nicotinamide dinucleotide (NADH) molecules are the first to enter the so-called electron transport chain or ETC of the mitochondria. The ETC represents a chain of reducing agents organized into four major protein-metal complexes (I-IV) that utilize the flow of electrons to drive the production of ATP. An additional integral protein that is related to oxidative phosphorylation is ATP synthase, referred to as complex V. Complex V carries out ATP synthesis as a result of the electron flow through the ETC. The coupling of electron flow from NADH to molecular oxygen to the production of ATP represents a process known as oxidative phosphorylation. In this review, we describe mainly the bioenergetic properties of mitochondria, such as those found in the ETC that may be altered in Alzheimer’s disease (AD). Increasing evidence points to several mitochondrial functions that are affected in AD. Furthermore, it is becoming apparent that mitochondria are a potential target for treatment in early-stage AD. With growing interest in the mitochondria as a target for AD, it has been hypothesized that deficit in this organelle may be at the heart of the progression of AD itself. The role of mitochondria in AD may be significant and is emerging as a main area of AD research.

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Notes

  1. Sections Introduction, General Mitochondrial Biochemistry, The Electron Transport System, The Chemiosmotic Theory of Bioenergetics heavily reference [1] unless otherwise indicated.

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Acknowledgments

This work was funded in part by the National Sciences and Engineering Research Council (to B.C.A.), the Everett Endowment Fund (to B.C.A.), the Edwards Family Endowment (to B.C.A.), the University of Manitoba (to C.C.), and the St. Boniface General Hospital Research Foundation (to B.C.A. and M. G. S.). B.C.A. is a Research Affiliate at the University of Manitoba’s Centre on Aging and holds the Honourable Douglas Everett, Patricia Everett and the Royal Canadian Properties Endowment Fund Chair and the Manitoba Dementia Research Chair.

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Authors and Affiliations

  1. St. Boniface Hospital Research, Winnipeg, MB, R2H 2A6, Canada

    Chris Cadonic, Mohammad Golam Sabbir & Benedict C. Albensi

  2. Graduate Program in Biomedical Engineering, Faculties of Health Sciences, Engineering, and Science, University of Manitoba, Winnipeg, MB, R3T 5V6, Canada

    Chris Cadonic & Benedict C. Albensi

  3. Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada

    Benedict C. Albensi

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  1. Chris Cadonic
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Correspondence to Chris Cadonic or Benedict C. Albensi.

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Cadonic, C., Sabbir, M.G. & Albensi, B.C. Mechanisms of Mitochondrial Dysfunction in Alzheimer’s Disease. Mol Neurobiol 53, 6078–6090 (2016). https://doi.org/10.1007/s12035-015-9515-5

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  • DOI: https://doi.org/10.1007/s12035-015-9515-5

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