The Properties of Amyloid-β Fibrils Are Determined by their Path of Formation

Brännström, Kristoffer; Islam, Tohidul; Gharibyan, Anna L.; Iakovleva, Irina; Nilsson, Lina; Lee, Cheng Choo; Sandblad, Linda; Pamrén, Annelie; Olofsson, Anders

doi:10.1016/j.jmb.2018.05.001

Cited by 22 publications

(29 citation statements)

References 48 publications

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“…Previously we have demonstrated that in case of cross-seeding of different environment-induced conformations of prion protein amyloid fibrils, the conformational template can self-propagate only via elongation mechanism, while surface induced nucleation only speeds up the aggregation process, but the conformation is defined by the environment conditions (Sneideris, Milto, and Smirnovas 2015). Recently similar observations were reported on amyloid beta (Brännström et al 2018) and alpha synuclein (Peduzzo, Linse, and Buell 2019). Our cross-environment seeding data on insulin follows the same path.…”

Section: Discussionsupporting

confidence: 81%

Peer Review #3 of "Concentration-dependent polymorphism of insulin amyloid fibrils (v0.1)"

2019

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Protein aggregation into highly structured fibrils has long been associated with several neurodegenerative disorders, such as Alzheimer's or Parkinson's disease. Polymorphism of amyloid fibrils increases the complexity of disease mechanisms and may be one of the reasons for the slow progress in drug research. Here we report protein concentration as another factor leading to polymorphism of insulin amyloid fibrils. Moreover, our data suggests that insulin amyloid conformation can self-replicate only via elongation, while seed-induced nucleation will lead to environment-defined conformation of fibrils. As similar observations were already described for a couple of other amyloid proteins, we suggest it to be a generic mechanism for self-replication of different amyloid fibril conformations.

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Section: Discussionsupporting

confidence: 81%

Peer Review #3 of "Concentration-dependent polymorphism of insulin amyloid fibrils (v0.1)"

2019

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“…Surface plasmon resonance presents a possibility to study the process of fibril formation because it can selectively probe the process of elongation without any significant influence from nucleation . By immobilizing mature Aβ 1–40 amyloid fibrils onto the SPR surface followed by probing with free monomers, the process of fibril‐templated polymerization can be monitored in detail.…”

Section: Resultsmentioning

confidence: 99%

Apolipoprotein E impairs amyloid‐β fibril elongation and maturation

et al. 2019

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Alzheimer’s disease (AD) is strongly linked to amyloid depositions of the Aβ peptide (Aβ). The lipid‐binding protein apolipoprotein E (ApoE) has been found to interfere with Aβ amyloid formation and to exert a strong clinical impact to the pathology of AD. The APOE gene exists in three allelic isoforms represented by APOE ε2, APOE ε3, and APOE ε4. Carriers of the APOE ε4 variant display a gene dose‐dependent increased risk of developing the disease. Aβ amyloids are formed via a nucleation‐dependent mechanism where free monomers are added onto a nucleus in a template‐dependent manner. Using a combination of surface plasmon resonance and thioflavin‐T assays, we here show that ApoE can target the process of fibril elongation and that its interference effectively prevents amyloid maturation. We expose a complex equilibrium where the concentration of ApoE, Aβ monomers, and the amount of already formed Aβ fibrils will affect the relative proportion and formation rate of mature amyloids versus alternative assemblies. The result illustrates a mechanism which may affect both the clearance rate of Aβ assemblies in vivo and the population of cytotoxic Aβ assemblies.

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“…Fibril elongation is the main event that contributes to the growth of aggregate mass via the addition of individual monomers to nuclei/fibril ends, whereas secondary nucleation facilitates the proliferation of amyloid aggregates through the fibril-surface-induced formation of new growth competent nuclei. Elongating fibrils usually replicate the structure of the initial seed (with only a couple of exceptions of possible conformational switching reported [ 16 , 17 ]); however, there is increasing evidence suggesting that the structure of amyloid fibrils replicated via secondary nucleation route is dependent on the environment rather than on the template of seeds [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates

Šneideris

Žiaunys

Chu

et al. 2020

IJMS

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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.

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The Properties of Amyloid-β Fibrils Are Determined by their Path of Formation

Cited by 22 publications

References 48 publications

Peer Review #3 of "Concentration-dependent polymorphism of insulin amyloid fibrils (v0.1)"

Peer Review #3 of "Concentration-dependent polymorphism of insulin amyloid fibrils (v0.1)"

Apolipoprotein E impairs amyloid‐β fibril elongation and maturation

Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates

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