Interactions between pathological and functional amyloid: A match made in Heaven or Hell? DOI Creative Commons
Daniel E. Otzen, Samuel Peña‐Díaz,

J J Widmann

et al.

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 103, P. 101351 - 101351

Published: March 1, 2025

The amyloid state of proteins occurs in many different contexts Nature and modern society, ranging from the pathological kind (neurodegenerative diseases amyloidosis) via man-made forms (food processing - to a much smaller extent protein biologics) functional versions (bacterial biofilm, peptide hormones signal transmission). These classes all come together human body which endogenously produces amyloidogenic able form (PaHA), hosts microbiome continuously makes bacterial (FuBA) ingests food can contain amyloid. This have grave consequences, given that PaHA spread throughout "hand-me-down" fashion cell through small fragments, kick-start growth new wherever they encounter monomeric precursors. Amyloid also self- cross-seed across dissimilar sequences. While it is very unlikely ingested plays role this crosstalk, FuBA-PaHA interactions are increasingly implicated vivo propagation. We now position understand structural bioinformatic basis for cross-talk, thanks recently obtained atomic-level structures two major FuBAs CsgA (E. coli) FapC (Pseudomonas). there reports homology-driven heterotypic between PaHA, proteome does not harbor significant homology FapC. Yet we others uncovered cross-stimulation (and some cases inhibition) FuBA both vitro vivo, here rationalize based on structure sequence. important consequences transmission development neurodegenerative diseases, least because into contact gut-brain interface, recurrent infections with microbes potentially even invasive biofilm brain. Whether first interact gut or brain, stimulate block each other's aggregation as well trigger inflammatory responses. may affect amyloidogenesis other ways, e.g. their own chaperones recognize show experimentally computationally. Heterotypic within vital part phenomenon constitute vibrant exciting frontier future research.

Language: Английский

Interactions between pathological and functional amyloid: A match made in Heaven or Hell? DOI Creative Commons
Daniel E. Otzen, Samuel Peña‐Díaz,

J J Widmann

et al.

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 103, P. 101351 - 101351

Published: March 1, 2025

The amyloid state of proteins occurs in many different contexts Nature and modern society, ranging from the pathological kind (neurodegenerative diseases amyloidosis) via man-made forms (food processing - to a much smaller extent protein biologics) functional versions (bacterial biofilm, peptide hormones signal transmission). These classes all come together human body which endogenously produces amyloidogenic able form (PaHA), hosts microbiome continuously makes bacterial (FuBA) ingests food can contain amyloid. This have grave consequences, given that PaHA spread throughout "hand-me-down" fashion cell through small fragments, kick-start growth new wherever they encounter monomeric precursors. Amyloid also self- cross-seed across dissimilar sequences. While it is very unlikely ingested plays role this crosstalk, FuBA-PaHA interactions are increasingly implicated vivo propagation. We now position understand structural bioinformatic basis for cross-talk, thanks recently obtained atomic-level structures two major FuBAs CsgA (E. coli) FapC (Pseudomonas). there reports homology-driven heterotypic between PaHA, proteome does not harbor significant homology FapC. Yet we others uncovered cross-stimulation (and some cases inhibition) FuBA both vitro vivo, here rationalize based on structure sequence. important consequences transmission development neurodegenerative diseases, least because into contact gut-brain interface, recurrent infections with microbes potentially even invasive biofilm brain. Whether first interact gut or brain, stimulate block each other's aggregation as well trigger inflammatory responses. may affect amyloidogenesis other ways, e.g. their own chaperones recognize show experimentally computationally. Heterotypic within vital part phenomenon constitute vibrant exciting frontier future research.

Language: Английский

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