Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes
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...
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SAGE-Hindawi Access to Research
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087431/ |
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pubmed-30874312011-05-05 Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes Askarova, Sholpan Yang, Xiaoguang Lee, James C.-M. Review Article 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 the mechanisms 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. SAGE-Hindawi Access to Research 2011-03-17 /pmc/articles/PMC3087431/ /pubmed/21547213 http://dx.doi.org/10.4061/2011/134971 Text en Copyright © 2011 Sholpan Askarova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Askarova, Sholpan Yang, Xiaoguang Lee, James C.-M. |
| spellingShingle |
Askarova, Sholpan Yang, Xiaoguang Lee, James C.-M. Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| author_facet |
Askarova, Sholpan Yang, Xiaoguang Lee, James C.-M. |
| author_sort |
Askarova, Sholpan |
| title |
Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| title_short |
Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| title_full |
Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| title_fullStr |
Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| title_full_unstemmed |
Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes |
| title_sort |
impacts of membrane biophysics in alzheimer's disease: from amyloid precursor protein processing to aβ peptide-induced membrane changes |
| description |
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 the mechanisms 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. |
| publisher |
SAGE-Hindawi Access to Research |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087431/ |
| _version_ |
1611451744437403648 |