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The Role of the Plasma Membrane Redox System in the Pathogenesis of Alzheimer’s Disease

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Studies on Alzheimer's Disease

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Abstract

Biological ageing is characterised by prolonged cellular damage over the lifespan, which results from oxidative stress processes that are implicated in both the initiation and progression of age-related disorders such as Alzheimer’s disease (AD). Recently, the role of the plasma membrane redox system, which consists of at least three major components: the lipophilic antioxidants (Coenzyme Q (CoQ) and α-tocopherol), the intracellular cytosolic electron donor (NAD(P)H) and membrane-associated quinone reductases (cytochrome b5 reductase and NADH-quinone), in protecting against oxidative stress has come into focus. Research shows that this redox system plays a protective role during mitochondrial dysfunction by aiding in the alternative glycolytic ATP production pathway and reducing oxidative stress. The different aspects of the plasma membrane operate in tandem to protect the membrane from lipid peroxidation, preventing the formation of semiquinone free radicals and reactive oxygen species, and to ultimately limit oxidative stress while still maintaining cellular levels of each component. Past studies have made a link between the plasma membrane redox system and AD and have revealed that each aspect is affected during the disease. Moreover, research has revealed that manipulating the system components can protect cells from amyloid-β toxicity, suggesting a key role in cell survival. To date, the relationship of the plasma membrane redox system to the brain changes seen in AD has yet to be fully elucidated, and we will review the current literature here.

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Acknowledgements

P.A.A. and D.I.F. are paid consultants, and shareholders, of Prana Biotechnology Ltd, and A.I.B. is a shareholder of Prana Biotechnology Ltd. P.A.A., D.I.F. and A.I.B. are primarily supported by the National Health and Medical Research Council and the Australian Research Council, and P.A.A. and D.I.F. are also supported by the Joan and Peter Clemenger Trust.

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Authors and Affiliations

  1. Synaptic Neurobiology Laboratory, The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, 30 Royal Pde, Parkville, VIC, 3052, Australia

    Sara M. Hancock Ph.D. & Paul A. Adlard Ph.D.

  2. Parkinson’s Disease Laboratory, The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, 30 Royal Pde, Parkville, VIC, 3052, Australia

    David I. Finkelstein Ph.D.

  3. Oxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, 30 Royal Pde, Parkville, VIC, 3052, Australia

    Ashley I. Bush Ph.D.

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  1. Sara M. Hancock Ph.D.
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  3. Ashley I. Bush Ph.D.
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Correspondence to Paul A. Adlard Ph.D. .

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Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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© 2013 Springer Science+Business Media New York

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Hancock, S.M., Finkelstein, D.I., Bush, A.I., Adlard, P.A. (2013). The Role of the Plasma Membrane Redox System in the Pathogenesis of Alzheimer’s Disease. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_6

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