Modulation of amyloid assembly by glycosaminoglycans: from mechanism to biological significance

Quittot, Noé; Sebastiao, Mathew; Bourgault, Steve

doi:10.1139/bcb-2016-0236

Cited by 33 publications

(39 citation statements)

References 96 publications

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“…HS chains can participate in both the nucleation or latency phase (‘lag phase’), and in the polymerization phase (growth phase). In the first stage, they allow the formation of a nucleus of monomers, and in the second phase they promote a rapid extension of protofibrils and formation of amyloid fibrils .…”

Section: Protein Aggregationmentioning

confidence: 99%

The role of heparan sulfates in protein aggregation and their potential impact on neurodegeneration

et al. 2018

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Neurodegenerative disorders, such as Alzheimer's, Parkinson's, and prion diseases, are directly linked to the formation and accumulation of protein aggregates in the brain. These aggregates, principally made of proteins or peptides that clamp together after acquisition of β-folded structures, also contain heparan sulfates. Several lines of evidence suggest that heparan sulfates centrally participate in the protein aggregation process. In vitro, they trigger misfolding, oligomerization, and fibrillation of amyloidogenic proteins, such as Aβ, tau, α-synuclein, prion protein, etc. They participate in the stabilization of protein aggregates, protect them from proteolysis, and act as cell-surface receptors for the cellular uptake of proteopathic seeds during their spreading. This review focuses attention on the importance of heparan sulfates in protein aggregation in brain disorders including Alzheimer's, Parkinson's, and prion diseases. The presence of these sulfated polysaccharides in protein inclusions in vivo and their capacity to trigger protein aggregation in vitro strongly suggest that they might play critical roles in the neurodegenerative process. Further advances in glyco-neurobiology will improve our understanding of the molecular and cellular mechanisms leading to protein aggregation and neurodegeneration.

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Section: Protein Aggregationmentioning

confidence: 99%

The role of heparan sulfates in protein aggregation and their potential impact on neurodegeneration

et al. 2018

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“…13–18 The aggregation depends on several factors, such as the length of the polysaccharides, 14,16 the nature and the degree of functionalization (e.g., sulfation), 13 and the ratio of the GAGs to the amyloid. 19 Short polysaccharides (DP < 5) show a very minimal effect on the rate of amyloid fibrillation, which increases with increasing chain length and ultimately reaches a maximum at high chain lengths (DP ≫ 18).…”

Section: Introductionmentioning

confidence: 99%

Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation

Das¹,

Dean²,

Fogel³

et al. 2017

Biomacromolecules

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GM1 ganglioside is known to promote amyloid-β (Aβ) peptide aggregation in Alzheimer’s disease. The roles of the individual saccharides and their distribution in this process are not understood. Acrylamide-based glycomonomers with either β-d-glucose or β-d-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via 1H NMR and electrospray ionization mass spectrometry. Glycopolymers of different molecular weights were synthesized by aqueous reversible addition–fragmentation chain transfer (aRAFT) polymerization and characterized by NMR and GPC. The polymers were used as models to investigate the effects of molecular weight and saccharide unit type on Aβ aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (~350 DP) glucose-containing glycopolymers had a profound effect on Aβ aggregation, promoting formation of soluble oligomers of Aβ and limiting fibril production, while the other glycopolymers and negative control had little effect on the Aβ propagation process.

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“…Peptide self‐assembly into well‐organized amyloid structures is commonly ascribed to a nucleated polymerization process, which is characterized by a sigmoidal growth divided in 3 phases: the nucleation phase (or lag phase), the elongation phase, and the saturation phase (Figure ) . The nucleation phase is characterized by the rate‐limiting formation of a nucleus, which results from the fast equilibrium between monomers that are assembly competent or not .…”

Section: Amyloid Structure and Self‐assemblymentioning

confidence: 99%

Amyloid self‐assembling peptides: Potential applications in nanovaccine engineering and biosensing

et al. 2018

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Living organisms are an inestimable source of inspiration for the design of biomaterials and nanostructures for medical and technological applications. Amyloids, which were historically associated with diseases, have recently been recognized as a biological structure that performs vital physiological functions in host organisms, highlighting their potential as life‐inspired assemblies. Amyloids are highly organized proteinaceous assemblies characterized by a cross‐β‐sheet quaternary conformation. The mechanical, physical, and biological properties of amyloids suggest that these nanostructures hold great potential as soft materials, nanoparticles, and biomatrices. This potential is associated with many characteristics, including the spontaneous self‐assembly of many polypeptide sequences, high mechanical resistance, biocompatibility, biodegradability as well as thermal, chemical, and enzymatic stability. Moreover, peptide‐based amyloid assemblies can efficiently be obtained by standard solid phase peptide synthesis and orthogonally functionalized with a wide range of biomolecules, such as large proteins and DNA. In this review, after briefly introducing the amyloid structure and the mechanisms of self‐assembly, we describe approaches to identify and design short self‐assembling amyloidogenic peptides. Afterward, we introduce strategies used to functionalize amyloid materials and we highlight some relevant examples in the development of nanovaccines and biosensors.

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Modulation of amyloid assembly by glycosaminoglycans: from mechanism to biological significance

Cited by 33 publications

References 96 publications

The role of heparan sulfates in protein aggregation and their potential impact on neurodegeneration

The role of heparan sulfates in protein aggregation and their potential impact on neurodegeneration

Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation

Amyloid self‐assembling peptides: Potential applications in nanovaccine engineering and biosensing

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