Structure and Aggregation Mechanisms in Amyloids
Chemistry Department and Coimbra Chemistry Centre, Faculty of Sciences and Technology, University of Coimbra, 3004-535 Coimbra, Portugal
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Academic Editor: Botond Penke
Molecules 2020, 25(5), 1195; https://doi.org/10.3390/molecules25051195
Received: 15 January 2020
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Revised: 17 February 2020
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Accepted: 19 February 2020
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Published: 6 March 2020
(This article belongs to the Special Issue Amyloids in Neurodegenerative Diseases)
The aggregation of a polypeptide chain into amyloid fibrils and their accumulation and deposition into insoluble plaques and intracellular inclusions is the hallmark of several misfolding diseases known as amyloidoses. Alzheimer′s, Parkinson′s and Huntington’s diseases are some of the approximately 50 amyloid diseases described to date. The identification and characterization of the molecular species critical for amyloid formation and disease development have been the focus of intense scrutiny. Methods such as X-ray and electron diffraction, solid-state nuclear magnetic resonance spectroscopy (ssNMR) and cryo-electron microscopy (cryo-EM) have been extensively used and they have contributed to shed a new light onto the structure of amyloid, revealing a multiplicity of polymorphic structures that generally fit the cross-β amyloid motif. The development of rational therapeutic approaches against these debilitating and increasingly frequent misfolding diseases requires a thorough understanding of the molecular mechanisms underlying the amyloid cascade. Here, we review the current knowledge on amyloid fibril formation for several proteins and peptides from a kinetic and thermodynamic point of view, the structure of the molecular species involved in the amyloidogenic process, and the origin of their cytotoxicity.
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Keywords:
misfolding diseases; amyloidosis; oligomers; aggregates; aggregation; aggregation mechanisms; steric zipper; amyloid fibrils; amyloid structure; amyloid dyes
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MDPI and ACS Style
Almeida, Z.L.; Brito, R.M.M. Structure and Aggregation Mechanisms in Amyloids. Molecules 2020, 25, 1195. https://doi.org/10.3390/molecules25051195
AMA Style
Almeida ZL, Brito RMM. Structure and Aggregation Mechanisms in Amyloids. Molecules. 2020; 25(5):1195. https://doi.org/10.3390/molecules25051195
Chicago/Turabian StyleAlmeida, Zaida L., and Rui M. M. Brito. 2020. "Structure and Aggregation Mechanisms in Amyloids" Molecules 25, no. 5: 1195. https://doi.org/10.3390/molecules25051195
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