Choi, ML;
Gandhi, S;
(2018)
Crucial role of protein oligomerization in the pathogenesis of Alzheimer's and Parkinson's diseases.
The FEBS Journal
, 285
(19)
pp. 3631-3644.
10.1111/febs.14587.
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Abstract
Misfolding and aggregation of the proteins amyloid-β (Aβ), tau and alpha-synuclein (α-syn) is the predominant pathology underlying the neurodegenerative disorders, Alzheimer's and Parkinson's disease. Whilst end stage insoluble products of aggregation have been well characterised in human and animal models of disease, accumulating evidence from biophysical, cellular and in vivo studies has shown that soluble intermediates of aggregation, or oligomers, may be the key species that mediate toxicity and underlie seeding and spreading in disease. Here we review the process of protein misfolding, and the intrinsic and extrinsic processes that cause the native states of the key aggregating proteins to undergo conformational change to form oligomers and ultimately fibrils. We discuss the structural features of the key toxic intermediate, and describe the putative mechanisms by which oligomers may cause cell toxicity. Finally we explore the potential therapeutic approaches raised by the oligomer hypothesis in neurodegenerative disease. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Crucial role of protein oligomerization in the pathogenesis of Alzheimer's and Parkinson's diseases |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/febs.14587 |
| Publisher version: | http://dx.doi.org/10.1111/febs.14587 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Alzheimer's disease, Parkinson's disease, alpha-synuclein, amyloid-β, oligomer, protein misfolding, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10051918 |
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