Impacts of membrane biophysics in Alzheimer’s disease: from amyloid precursor protein processing to Aβ peptide-induced membrane changes
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Date
2011-01-21
Authors
Askarova, Sholpan
Yang, Xiaoguang
Lee, James C-M.
Journal Title
Journal ISSN
Volume Title
Publisher
SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease
Abstract
An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer’s disease (AD), are strongly associated with its ability to interact with membranes of neurons and
other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding themechanisms leading to changes in a membrane’s biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD.
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Keywords
Research Subject Categories::TECHNOLOGY::Bioengineering, regenerative medicine, Research Subject Categories::MEDICINE::Physiology and pharmacology::Physiology::Neurophysiology