scholarly journals An Azobenzene Photoswitch Sheds Light on Turn Nucleation in Amyloid-β Self-Assembly

2012 ◽  
Vol 3 (3) ◽  
pp. 211-220 ◽  
Author(s):  
Todd M. Doran ◽  
Elizabeth A. Anderson ◽  
Sarah E. Latchney ◽  
Lisa A. Opanashuk ◽  
Bradley L. Nilsson
Keyword(s):  
Self Assembly ◽  
Amyloid Β

scholarly journals An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Devkee M. Vadukul ◽  
Céline Vrancx ◽  
Pierre Burguet ◽  
Sabrina Contino ◽  
Nuria Suelves ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Self Assembly ◽  
Critical Nucleus ◽  
Amyloid Fibril ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
The Self ◽  
Aβ Peptide ◽  
Amyloid Fibril Formation ◽  
Secretase Activity

AbstractA key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.

Hydrophobicity and Conformational Change as Mechanistic Determinants for Nonspecific Modulators of Amyloid β Self-Assembly

Biochemistry ◽  
2011 ◽  
Vol 51 (1) ◽  
pp. 126-137 ◽  
Author(s):  
Axel Abelein ◽  
Benedetta Bolognesi ◽  
Christopher M. Dobson ◽  
Astrid Gräslund ◽  
Christofer Lendel
Keyword(s):  
Conformational Change ◽  
Self Assembly ◽  
Amyloid Β

scholarly journals Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 925 ◽  
Author(s):  
Kristina Endres
Keyword(s):  
Neurodegenerative Diseases ◽  
Self Assembly ◽  
Amyloid Β ◽  
Degenerative Diseases ◽  
Human Beings ◽  
Precursor Proteins ◽  
Long Time ◽  
Health And Disease ◽  
Amyloidogenic Peptides ◽  
Toxic Peptides

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that microbes also possess amyloidogenic peptides is intriguing. Transmission of amyloids by iatrogenic means or by consumption of contaminated meat from diseased animals is a well-known fact. What if also our microbial commensals might drive human amyloidosis or suffer from our aggregated amyloids? Moreover, as the microbial amyloids are evolutionarily older, we might learn from these organisms how to cope with the sword of Damocles forged of endogenous, potentially toxic peptides. This review summarizes knowledge about the interplay between human amyloids involved in neurodegenerative diseases and microbial amyloids.

scholarly journals Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2316 ◽  
Author(s):  
Qiuchen Zheng ◽  
Micheal T. Kebede ◽  
Merc M. Kemeh ◽  
Saadman Islam ◽  
Bethany Lee ◽  
...  
Keyword(s):  
Self Assembly ◽  
Complex Disease ◽  
Red Wine ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Therapeutic Agents ◽  
Mechanistic Studies ◽  
Naturally Occurring ◽  
Aβ Oligomerization ◽  
Β Sheet

The amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer’s disease (AD). Both Aβ and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of Aβ and tau. Polyphenols modulate the enzymatic processing of the amyloid-β precursor protein and inhibit toxic Aβ oligomerization by enhancing the clearance of Aβ42 monomer, modulating monomer–monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau β-sheet formation. The anti-Aβ-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms.

scholarly journals Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1983 ◽  
Author(s):  
Jennifer M. Urban ◽  
Janson Ho ◽  
Gavin Piester ◽  
Riqiang Fu ◽  
Bradley L. Nilsson
Keyword(s):  
Sequence Space ◽  
Self Assembly ◽  
Solid State Nmr ◽  
Amyloid Β ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid ◽  
Amphipathic Peptide ◽  
Sequence Patterns ◽  
Β Sheets ◽  
Β Sheet

In 1953, Pauling and Corey predicted that enantiomeric β-sheet peptides would coassemble into so-called “rippled” β-sheets, in which the β-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-β (Aβ) peptide that does not follow this sequence pattern, amyloid-β (16–22), readily coassembles into rippled β-sheets. Equimolar mixtures of enantiomeric amyloid-β (16–22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated β-sheet fibrils. Formation of rippled β-sheets composed of alternating l- and d-amyloid-β (16–22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled β-sheet formation by l- and d-amyloid-β (16–22) is energetically favorable relative to self-assembly into corresponding pleated β-sheets. This work illustrates that coassembly of enantiomeric β-sheet peptides into rippled β-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled β-sheet materials.

Enhanced self-assembly of the 7–12 sequence of amyloid-β peptide by tyrosine bromination

2020 ◽  
Vol 32 (4) ◽  
pp. 247-255 ◽  
Author(s):  
Daniele Maiolo ◽  
Andrea Pizzi ◽  
Alessandro Gori ◽  
Greta Bergamaschi ◽  
Claudia Pigliacelli ◽  
...  
Keyword(s):  
Self Assembly ◽  
Amyloid Β ◽  
Amyloid Β Peptide

scholarly journals Aβ(M1–40) and Wild-Type Aβ40 Self-Assemble into Oligomers with Distinct Quaternary Structures

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2242 ◽  
Author(s):  
Jacob L. Bouchard ◽  
Taylor C. Davey ◽  
Todd M. Doran
Keyword(s):  
Self Assembly ◽  
Quaternary Structure ◽  
Biological Activities ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Wild Type ◽  
Molecular Weights ◽  
Term Potentiation ◽  
Quaternary Structures

Amyloid-β oligomers (AβOs) self-assemble into polymorphic species with diverse biological activities that are implicated causally to Alzheimer’s disease (AD). Synaptotoxicity of AβO species is dependent on their quaternary structure, however, low-abundance and environmental sensitivity of AβOs in vivo have impeded a thorough assessment of structure–function relationships. We developed a simple biochemical assay to quantify the relative abundance and morphology of cross-linked AβOs. We compared oligomers derived from synthetic Aβ40 (wild-type (WT) Aβ40) and a recombinant source, called Aβ(M1–40). Both peptides assemble into oligomers with common sizes and morphology, however, the predominant quaternary structures of Aβ(M1–40) oligomeric states were more diverse in terms of dispersity and morphology. We identified self-assembly conditions that stabilize high-molecular weight oligomers of Aβ(M1–40) with apparent molecular weights greater than 36 kDa. Given that mixtures of AβOs derived from both peptides have been shown to be potent neurotoxins that disrupt long-term potentiation, we anticipate that the diverse quaternary structures reported for Aβ(M1–40) oligomers using the assays reported here will facilitate research efforts aimed at isolating and identifying common toxic species that contribute to synaptic dysfunction.

scholarly journals Lipid membranes trigger misfolding and self-assembly of amyloid β 42 protein into aggregates

2019 ◽  
Author(s):  
Siddhartha Banerjee ◽  
Mohtadin Hashemi ◽  
Karen Zagorski ◽  
Yuri L. Lyubchenko
Keyword(s):  
Self Assembly ◽  
Lipid Membranes ◽  
Membrane Surface ◽  
Amyloid Β ◽  
Test Tube ◽  
Aggregation Process ◽  
Self Assembling ◽  
Nanoscale Aggregates

AbstractThe assembly of polypeptides and proteins into nanoscale aggregates is a phenomenon observed in a vast majority of proteins. Importantly, aggregation of amyloid β (Aβ) proteins is considered as a major cause for the development of Alzheimer’s disease. The process depends on various conditions and typical test-tube experiments require high protein concentration that complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here we demonstrate that Aβ42 monomers at the membrane bilayer are capable of self-assembling into aggregates at physiologically low concentrations, and the membrane in this aggregation process plays a role of a catalyst. We applied all-atom molecular dynamics to demonstrate that the interaction with the membrane surface dramatically changes the conformation of Aβ42 protein. As a result, the misfolded Aβ42 rapidly assembles into dimers, trimers and tetramers, so the on-surface aggregation is the mechanism by which amyloid oligomers are produced and spread.

scholarly journals Reproducibility Problems of Amyloid-β Self-Assembly and How to Deal With Them

2021 ◽  
Vol 8 ◽  
Author(s):  
Peter Faller ◽  
Christelle Hureau
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Self Assembly ◽  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Test Tube ◽  
The Self ◽  
Aggregation Process ◽  
Self Assembled

The self-assembly of peptides and proteins into amyloid fibrils and other aggregates are linked to several diseases. One of the most studied cases is the peptide amyloid-β (Aβ), found self-assembled in Alzheimer's disease patients' brains. In test tubes, assays with chemically synthesized or recombinant Aβ are widely investigated to understand the aggregation process and to find modulators, which could be of therapeutic interest. Experience over more than a decade in our laboratory through discussions with colleagues, expertly studying the literature, and as reviewers revealed to us the widely encountered difficulty to control the aggregation and obtain reproducible results in the test tube. However, this issue is scarcely reported and discussed in the publications, which we think hampers strongly the progress in this field and can deceive newcomers. Here, we describe the difficulty and potential reasons to obtain reproducible aggregation data and propose some guidelines for working with it.

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