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Biology
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Biophysics of Amyloid Aggregation
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Biophysics of Amyloid Aggregation

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biophysics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 10330

Special Issue Editors

Prof. Dr. Michele Vendruscolo

E-Mail Website
Guest Editor
Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Interests: protein folding; protein misfolding; protein aggregation; protein homeostasis; protein misfolding diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Ryan Limbocker

E-Mail Website
Guest Editor
Department of Chemistry and Life Science, United States Military Academy, West Point, NY 10996, USA
Interests: protein misfolding diseases; protein aggregation; biophysics; biotoxin countermeasures design

Special Issue Information

Dear Colleagues,

The amyloid state is associated with human conditions that are still incurable and becoming increasingly prevalent, such as Alzheimer’s and Parkinson’s diseases and type II diabetes. In these diseases, a range of peptides and proteins aberrantly convert from their soluble native states into intractable amyloid aggregates that disrupt cellular functions. To design effective therapeutics to prevent, delay or combat these devastating pathologies, it is important to further resolve the fundamental processes underpinning the aggregation reactions of specific biomolecules. In this Special Issue, we invite contributions that leverage biophysical approaches to study the fundamental biology and chemistry underlying protein aggregation in neurodegenerative diseases. All submissions that extend our knowledge of the amyloid state and its links to pathology are welcome. Examples of topics include, but are not limited to, disease models, diagnostics, drug discovery, antibody discovery, structural biology, chemical kinetics, structure-toxicity relationships, and high-resolution imaging.

Prof. Dr. Michele Vendruscolo
Dr. Ryan Limbocker
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • protein aggregation
  • amyloid toxicity
  • protein misfolding diseases
  • Alzheimer’s disease
  • Parkinson’s disease
  • chronic traumatic encephalopathy
  • traumatic brain injury
  • biophysics and molecular biology
  • animal models
  • drug discovery or antibody design
  • diagnostics
  • structural studies at high resolution

Published Papers (3 papers)

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Research

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13 pages, 1885 KiB  
Article
Small Angle X-ray Scattering Sensing Membrane Composition: The Role of Sphingolipids in Membrane-Amyloid β-Peptide Interaction
by Rita Carrotta, Maria Rosalia Mangione, Fabio Librizzi and Oscar Moran
Biology 2022, 11(1), 26; https://doi.org/10.3390/biology11010026 - 25 Dec 2021
Cited by 3 | Viewed by 2392
Abstract
The early impairments appearing in Alzheimer’s disease are related to neuronal membrane damage. Both aberrant Aβ species and specific membrane components play a role in promoting aggregation, deposition, and signaling dysfunction. Ganglioside GM1, present with cholesterol and sphingomyelin in lipid rafts, preferentially interacts [...] Read more.
The early impairments appearing in Alzheimer’s disease are related to neuronal membrane damage. Both aberrant Aβ species and specific membrane components play a role in promoting aggregation, deposition, and signaling dysfunction. Ganglioside GM1, present with cholesterol and sphingomyelin in lipid rafts, preferentially interacts with the Aβ peptide. GM1 at physiological conditions clusters in the membrane, the assembly also involves phospholipids, sphingomyelin, and cholesterol. The structure of large unilamellar vesicles (LUV), made of a basic POPC:POPS matrix in a proportion of 9:1, and containing different amounts of GM1 (1%, 3%, and 4% mol/mol) in the presence of 5% mol/mol sphingomyelin and 15% mol/mol cholesterol, was studied using small angle X-ray scattering (SAXS). The effect of the membrane composition on the LUVs–Aβ-peptide interaction, both for Aβ1–40 and Aβ1–42 variants, was, thus, monitored. The presence of GM1 leads to a significant shift of the main peak, towards lower scattering angles, up to 6% of the initial value with SM and 8% without, accompanied by an opposite shift of the first minimum, up to 21% and 24% of the initial value, respectively. The analysis of the SAXS spectra, using a multi-Gaussian model for the electronic density profile, indicated differences in the bilayer of the various compositions. An increase in the membrane thickness, by 16% and 12% when 2% and 3% mol/mol GM1 was present, without and with SM, respectively, was obtained. Furthermore, in these cases, in the presence of Aβ40, a very small decrease of the bilayer thickness, less than 4% and 1%, respectively, was derived, suggesting the inhibiting effect that the presence of sphingomyelin has on the GM1–Aβ interaction. Full article
(This article belongs to the Special Issue Biophysics of Amyloid Aggregation)
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14 pages, 2726 KiB  
Article
The Amyloid Region of Hfq Riboregulator Promotes DsrA:rpoS RNAs Annealing
by Florian Turbant, Pengzhi Wu, Frank Wien and Véronique Arluison
Biology 2021, 10(9), 900; https://doi.org/10.3390/biology10090900 - 12 Sep 2021
Cited by 7 | Viewed by 2212
Abstract
Hfq is a bacterial RNA chaperone which promotes the pairing of small noncoding RNAs to target mRNAs, allowing post-transcriptional regulation. This RNA annealing activity has been attributed for years to the N-terminal region of the protein that forms a toroidal structure with a [...] Read more.
Hfq is a bacterial RNA chaperone which promotes the pairing of small noncoding RNAs to target mRNAs, allowing post-transcriptional regulation. This RNA annealing activity has been attributed for years to the N-terminal region of the protein that forms a toroidal structure with a typical Sm-fold. Nevertheless, many Hfqs, including that of Escherichia coli, have a C-terminal region with unclear functions. Here we use a biophysical approach, Synchrotron Radiation Circular Dichroism (SRCD), to probe the interaction of the E. coli Hfq C-terminal amyloid region with RNA and its effect on RNA annealing. This C-terminal region of Hfq, which has been described to be dispensable for sRNA:mRNA annealing, has an unexpected and significant effect on this activity. The functional consequences of this novel property of the amyloid region of Hfq in relation to physiological stress are discussed. Full article
(This article belongs to the Special Issue Biophysics of Amyloid Aggregation)
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Review

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14 pages, 1965 KiB  
Review
Proteins Do Not Replicate, They Precipitate: Phase Transition and Loss of Function Toxicity in Amyloid Pathologies
by Kariem Ezzat, Andrea Sturchio and Alberto J. Espay
Biology 2022, 11(4), 535; https://doi.org/10.3390/biology11040535 - 30 Mar 2022
Cited by 16 | Viewed by 4838
Abstract
Protein aggregation into amyloid fibrils affects many proteins in a variety of diseases, including neurodegenerative disorders, diabetes, and cancer. Physicochemically, amyloid formation is a phase transition process, where soluble proteins are transformed into solid fibrils with the characteristic cross-β conformation responsible for their [...] Read more.
Protein aggregation into amyloid fibrils affects many proteins in a variety of diseases, including neurodegenerative disorders, diabetes, and cancer. Physicochemically, amyloid formation is a phase transition process, where soluble proteins are transformed into solid fibrils with the characteristic cross-β conformation responsible for their fibrillar morphology. This phase transition proceeds via an initial, rate-limiting nucleation step followed by rapid growth. Several well-defined nucleation pathways exist, including homogenous nucleation (HON), which proceeds spontaneously; heterogeneous nucleation (HEN), which is catalyzed by surfaces; and seeding via preformed nuclei. It has been hypothesized that amyloid aggregation represents a protein-only (nucleic-acid free) replication mechanism that involves transmission of structural information via conformational templating (the prion hypothesis). While the prion hypothesis still lacks mechanistic support, it is also incompatible with the fact that proteins can be induced to form amyloids in the absence of a proteinaceous species acting as a conformational template as in the case of HEN, which can be induced by lipid membranes (including viral envelopes) or polysaccharides. Additionally, while amyloids can be formed from any protein sequence and via different nucleation pathways, they invariably adopt the universal cross-β conformation; suggesting that such conformational change is a spontaneous folding event that is thermodynamically favorable under the conditions of supersaturation and phase transition and not a templated replication process. Finally, as the high stability of amyloids renders them relatively inert, toxicity in some amyloid pathologies might be more dependent on the loss of function from protein sequestration in the amyloid state rather than direct toxicity from the amyloid plaques themselves. Full article
(This article belongs to the Special Issue Biophysics of Amyloid Aggregation)
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