Cargando…
Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease
The brains of Alzheimer’s disease (AD) patients contain numerous amyloid plaques that are diagnostic of the disease. The plaques are primarily composed of the amyloidogenic peptides proteins Aβ40 and Aβ42, which are derived by the processing of the amyloid pre-cursor protein (APP) by two proteases c...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781152/ https://www.ncbi.nlm.nih.gov/pubmed/36557940 http://dx.doi.org/10.3390/molecules27248804 |
_version_ | 1784857003861999616 |
---|---|
author | Rosenberry, Terrone L. Zhou, Huan-Xiang Stagg, Scott M. Paravastu, Anant K. |
author_facet | Rosenberry, Terrone L. Zhou, Huan-Xiang Stagg, Scott M. Paravastu, Anant K. |
author_sort | Rosenberry, Terrone L. |
collection | PubMed |
description | The brains of Alzheimer’s disease (AD) patients contain numerous amyloid plaques that are diagnostic of the disease. The plaques are primarily composed of the amyloidogenic peptides proteins Aβ40 and Aβ42, which are derived by the processing of the amyloid pre-cursor protein (APP) by two proteases called β-secretase and γ-secretase. Aβ42 differs from Aβ40 in having two additional hydrophobic amino acids, ILE and ALA, at the C-terminus. A small percentage of AD is autosomal dominant (ADAD) and linked either to the genes for the presenilins, which are part of γ-secretase, or APP. Because ADAD shares most pathogenic features with widespread late-onset AD, Aβ peptides have become the focus of AD research. Fibrils formed by the aggregation of these peptides are the major component of plaques and were initially targeted in AD therapy. However, the fact that the abundance of plaques does not correlate well with cognitive decline in AD patients has led investigators to examine smaller Aβ aggregates called oligomers. The low levels and heterogeneity of Aβ oligomers have made the determination of their structures difficult, but recent structure determinations of oligomers either formed or initiated in detergents have been achieved. We report here on the structures of these oligomers and suggest how they may be involved in AD. |
format | Online Article Text |
id | pubmed-9781152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97811522022-12-24 Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease Rosenberry, Terrone L. Zhou, Huan-Xiang Stagg, Scott M. Paravastu, Anant K. Molecules Review The brains of Alzheimer’s disease (AD) patients contain numerous amyloid plaques that are diagnostic of the disease. The plaques are primarily composed of the amyloidogenic peptides proteins Aβ40 and Aβ42, which are derived by the processing of the amyloid pre-cursor protein (APP) by two proteases called β-secretase and γ-secretase. Aβ42 differs from Aβ40 in having two additional hydrophobic amino acids, ILE and ALA, at the C-terminus. A small percentage of AD is autosomal dominant (ADAD) and linked either to the genes for the presenilins, which are part of γ-secretase, or APP. Because ADAD shares most pathogenic features with widespread late-onset AD, Aβ peptides have become the focus of AD research. Fibrils formed by the aggregation of these peptides are the major component of plaques and were initially targeted in AD therapy. However, the fact that the abundance of plaques does not correlate well with cognitive decline in AD patients has led investigators to examine smaller Aβ aggregates called oligomers. The low levels and heterogeneity of Aβ oligomers have made the determination of their structures difficult, but recent structure determinations of oligomers either formed or initiated in detergents have been achieved. We report here on the structures of these oligomers and suggest how they may be involved in AD. MDPI 2022-12-12 /pmc/articles/PMC9781152/ /pubmed/36557940 http://dx.doi.org/10.3390/molecules27248804 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Rosenberry, Terrone L. Zhou, Huan-Xiang Stagg, Scott M. Paravastu, Anant K. Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title | Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title_full | Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title_fullStr | Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title_full_unstemmed | Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title_short | Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer’s Disease |
title_sort | oligomer formation by amyloid-β42 in a membrane-mimicking environment in alzheimer’s disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781152/ https://www.ncbi.nlm.nih.gov/pubmed/36557940 http://dx.doi.org/10.3390/molecules27248804 |
work_keys_str_mv | AT rosenberryterronel oligomerformationbyamyloidb42inamembranemimickingenvironmentinalzheimersdisease AT zhouhuanxiang oligomerformationbyamyloidb42inamembranemimickingenvironmentinalzheimersdisease AT staggscottm oligomerformationbyamyloidb42inamembranemimickingenvironmentinalzheimersdisease AT paravastuanantk oligomerformationbyamyloidb42inamembranemimickingenvironmentinalzheimersdisease |