Numerous cardiorespiratory disorders result in persistent systemic hypoxia, or at worst (as a consequence of stroke) deprive the brain of oxygen completely for a period of time. Patients suffering from such conditions are much more susceptible to the development of dementias such as AD (Alzheimer’s disease). Until recently, the cellular and molecular basis for the predisposition to AD by systemic hypoxia has been completely unknown. However, emerging evidence suggests that pathological cellular remodelling caused by chronic hypoxia shows striking similarities to those observed in the central nervous system as a consequence of AD. Furthermore, prolonged hypoxia can induce formation of Aβs (amyloid β peptides), the primary neurotoxic elements of AD, which accumulate over years to form the extracellular plaques that are the hallmark feature of the disease. Hypoxia can lead to paradoxical increases in mitochondrial ROS (reactive oxygen species) generation upstream of Aβ formation. The downstream consequences of prolonged hypoxia include remodelling of functional expression of voltage-gated calcium channels and disturbance of intracellular calcium homoeostasis via disrupted calcium buffering and inhibition of calcium extrusion mechanisms. These effects can be mimicked by application of exogenous Aβ and, crucially, appear to depend on Aβ formation. Current knowledge supports the concept that prevention of the deleterious effects of hypoxia may prove beneficial in slowing or preventing the onset of AD.
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August 2007
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Review Article|
August 10 2007
Hypoxia and Alzheimer’s disease
Chris Peers;
Chris Peers
1
*Faculty of Medicine, University of Leeds, Leeds LS2 9JT, U.K.
1To whom correspondence should be addressed (email [email protected]).
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Hugh A. Pearson;
Hugh A. Pearson
†Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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John P. Boyle
John P. Boyle
*Faculty of Medicine, University of Leeds, Leeds LS2 9JT, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1358
Print ISSN: 0071-1365
© The Authors Journal compilation © 2007 Biochemical Society
2007
Essays Biochem (2007) 43: 153–164.
Citation
Chris Peers, Chris Peers, Hugh A. Pearson, John P. Boyle; Hypoxia and Alzheimer’s disease. Essays Biochem 10 August 2007; 43 153–164. doi: https://doi.org/10.1042/bse0430153
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