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Special Issue "Amyloid Hetero-Aggregation"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editors

Dr. Ludmilla A. Morozova-Roche
E-Mail Website
Guest Editor
Department of Medical Biochemistry and Biophsyics, Umeå Univeristy, Umeå, SE 90187, Sweden
Interests: biodiagnostics; amyloid; protein misfolding; neuroinflammation; cellular toxicity; neurodegenerative diseases; blood serum; CSF; bioimaging
Special Issues and Collections in MDPI journals
Dr. Himanshu Chaudhary
E-Mail Website
Guest Editor
Department of Chemistry and Molecular Biology Gothenburg University, Gothenburg, Sweden
Interests: amyloid, protein misfolding, protein aggregation, protein-protein interaction, protein−lipid interaction, lipid membranes, vesicles, blood serum and CSF, neurodegenerative diseases

Special Issue Information

Dear Colleagues,

This Special Issue will address the molecular and cellular mechanisms of amyloid hetero-aggregation, deposition, and toxicity of various proteins – human, bacterial, and viral. Studies conducted in vitro, in vivo, and ex vivo materials are welcome. Amyloid formation is a widespread phenomenon due to in the generic property of polypeptide chains that self-assemble into cross-β-sheet superstructures and are manifested in numerous amyloid-related diseases, as well as in functional amyloids. The amyloid cascade lies at the center of amyloid disease pathology, involved in up to 50 human diseases, though it is still debated if this is the cause or a consequence of disease. Amyloid formation in neurodegenerative disease and others is often associated with inflammation as a common denominator of those diseases. For example, inflammation triggers the massive production of proinflammatory S100A9 that spontaneously form amyloids and co-aggregates into hetero-amyloids together with Abeta or alpha-synuclein in Alzheimer’s or Parkinson’s disease, respectively. These events initiate the whole pathological amyloid cascade. Recently, the comorbidity of amyloid diseases was also shown to be linked to the co-aggregation of different amyloidogenic proteins. Since amyloids formed by individual polypeptides are highly polymorphic, their co-aggregates add up to the complexity and heterogeneity of the amyloid mixture. Despite the key clinical importance of amyloid formation, the mechanisms of co-aggregation of different amyloid species remain elusive. There is an unmet need to understand the architecture and mechanisms of self-assembly leading to the formation of hetero-aggregates composed of various amyloid polypeptides. Your research and review articles on this subject are very welcome in this issue.

Dr. Ludmilla A. Morozova-Roche
Dr. Himanshu Chaudhary
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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • amyloid
  • co-aggregation
  • hetero-aggregation
  • human proteins
  • bacterial amyloids
  • viral proteins
  • cytotoxicity
  • structure
  • function

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Published Papers (5 papers)

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Research

Article
S100A9 Alters the Pathway of Alpha-Synuclein Amyloid Aggregation
Int. J. Mol. Sci. 2021, 22(15), 7972; https://doi.org/10.3390/ijms22157972 - 26 Jul 2021
Viewed by 169
Abstract
The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Alpha-synuclein is the main protein found in neuronal inclusions of patients who have suffered from Parkinson’s [...] Read more.
The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Alpha-synuclein is the main protein found in neuronal inclusions of patients who have suffered from Parkinson’s disease. S100A9 is a calcium-binding, pro-inflammation protein, which is also found in such amyloid plaques. To understand the influence of S100A9 on the aggregation of α-synuclein, we analyzed their co-aggregation kinetics and the resulting amyloid fibril structure by Fourier-transform infrared spectroscopy and atomic force microscopy. We found that the presence of S100A9 alters the aggregation kinetics of α-synuclein and stabilizes the formation of a particular amyloid fibril structure. We also show that the solution’s ionic strength influences the interplay between S100A9 and α-synuclein, stabilizing a different structure of α-synuclein fibrils. Full article
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
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Article
Human Polymerase δ-Interacting Protein 2 (PolDIP2) Inhibits the Formation of Human Tau Oligomers and Fibrils
Int. J. Mol. Sci. 2021, 22(11), 5768; https://doi.org/10.3390/ijms22115768 - 28 May 2021
Viewed by 811
Abstract
A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) [...] Read more.
A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) interacts with Tau. With a set of complementary methods, including thioflavin-T-based aggregation kinetic assays, Tau oligomer-specific dot-blot analysis, and single oligomer/fibril analysis by atomic force microscopy, we demonstrate that PolDIP2 inhibits Tau aggregation and amyloid fibril growth in vitro. The identification of PolDIP2 as a potential regulator of cellular Tau aggregation should be considered for future Tau-targeting therapeutics. Full article
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
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Article
Lysozyme Fibrils Alter the Mechanism of Insulin Amyloid Aggregation
Int. J. Mol. Sci. 2021, 22(4), 1775; https://doi.org/10.3390/ijms22041775 - 10 Feb 2021
Viewed by 678
Abstract
Protein aggregation into amyloid fibrils is linked to multiple disorders. The understanding of how natively non-harmful proteins convert to these highly cytotoxic amyloid aggregates is still not sufficient, with new ideas and hypotheses being presented each year. Recently it has been shown that [...] Read more.
Protein aggregation into amyloid fibrils is linked to multiple disorders. The understanding of how natively non-harmful proteins convert to these highly cytotoxic amyloid aggregates is still not sufficient, with new ideas and hypotheses being presented each year. Recently it has been shown that more than one type of protein aggregates may co-exist in the affected tissue of patients suffering from amyloid-related disorders, sparking the idea that amyloid aggregates formed by one protein may induce another protein’s fibrillization. In this work, we examine the effect that lysozyme fibrils have on insulin amyloid aggregation. We show that not only do lysozyme fibrils affect insulin nucleation, but they also alter the mechanism of its aggregation. Full article
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
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Article
Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates
Int. J. Mol. Sci. 2020, 21(19), 7410; https://doi.org/10.3390/ijms21197410 - 08 Oct 2020
Cited by 1 | Viewed by 935
Abstract
Prion protein amyloid aggregates are associated with infectious neurodegenerative diseases, known as transmissible spongiform encephalopathies. Self-replication of amyloid structures by refolding of native protein molecules is the probable mechanism of disease transmission. Amyloid fibril formation and self-replication can be affected by many different [...] Read more.
Prion protein amyloid aggregates are associated with infectious neurodegenerative diseases, known as transmissible spongiform encephalopathies. Self-replication of amyloid structures by refolding of native protein molecules is the probable mechanism of disease transmission. Amyloid fibril formation and self-replication can be affected by many different factors, including other amyloid proteins and peptides. Mouse prion protein fragments 107-143 (PrP(107-143)) and 89-230 (PrP(89-230)) can form amyloid fibrils. β-sheet core in PrP(89-230) amyloid fibrils is limited to residues ∼160–220 with unstructured N-terminus. We employed chemical kinetics tools, atomic force microscopy and Fourier-transform infrared spectroscopy, to investigate the effects of mouse prion protein fragment 107-143 fibrils on the aggregation of PrP(89-230). The data suggest that amyloid aggregates of a short prion-derived peptide are not able to seed PrP(89-230) aggregation; however, they accelerate the self-replication of PrP(89-230) amyloid fibrils. We conclude that PrP(107-143) fibrils could facilitate the self-replication of PrP(89-230) amyloid fibrils in several possible ways, and that this process deserves more attention as it may play an important role in amyloid propagation. Full article
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
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Article
Characterization of the Relationship between the Chaperone and Lipid-Binding Functions of the 70-kDa Heat-Shock Protein, HspA1A
Int. J. Mol. Sci. 2020, 21(17), 5995; https://doi.org/10.3390/ijms21175995 - 20 Aug 2020
Cited by 2 | Viewed by 832
Abstract
HspA1A, a molecular chaperone, translocates to the plasma membrane (PM) of stressed and cancer cells. This translocation results in HspA1A’s cell-surface presentation, which renders tumors radiation insensitive. To specifically inhibit the lipid-driven HspA1A’s PM translocation and devise new therapeutics it is imperative to [...] Read more.
HspA1A, a molecular chaperone, translocates to the plasma membrane (PM) of stressed and cancer cells. This translocation results in HspA1A’s cell-surface presentation, which renders tumors radiation insensitive. To specifically inhibit the lipid-driven HspA1A’s PM translocation and devise new therapeutics it is imperative to characterize the unknown HspA1A’s lipid-binding regions and determine the relationship between the chaperone and lipid-binding functions. To elucidate this relationship, we determined the effect of phosphatidylserine (PS)-binding on the secondary structure and chaperone functions of HspA1A. Circular dichroism revealed that binding to PS resulted in minimal modification on HspA1A’s secondary structure. Measuring the release of inorganic phosphate revealed that PS-binding had no effect on HspA1A’s ATPase activity. In contrast, PS-binding showed subtle but consistent increases in HspA1A’s refolding activities. Furthermore, using a Lysine-71-Alanine mutation (K71A; a null-ATPase mutant) of HspA1A we show that although K71A binds to PS with affinities similar to the wild-type (WT), the mutated protein associates with lipids three times faster and dissociates 300 times faster than the WT HspA1A. These observations suggest a two-step binding model including an initial interaction of HspA1A with lipids followed by a conformational change of the HspA1A-lipid complex, which accelerates the binding reaction. Together these findings strongly support the notion that the chaperone and lipid-binding activities of HspA1A are dependent but the regions mediating these functions do not overlap and provide the basis for future interventions to inhibit HspA1A’s PM-translocation in tumor cells, making them sensitive to radiation therapy. Full article
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
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