Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked? DOI Creative Commons
Anna Duda-Madej, Jakub Stecko, Natalia Szymańska

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 8, 2024

Crohn’s disease (CD) is a chronic inflammatory that most frequently affects part of the distal ileum, but it may affect any gastrointestinal tract. CD also be related to systemic inflammation and extraintestinal manifestations. Alzheimer’s (AD) common neurodegenerative disease, gradually worsening behavioral cognitive functions. Despite meaningful progress, both diseases are still incurable have not fully explained, heterogeneous pathomechanism includes immunological, microbiological, genetic, environmental factors. Recently, emerging evidence indicates condition corresponds an increased risk diseases, intestinal inflammation, including CD, increases AD. Even though now known AD, exact pathways connecting these two seemingly unrelated remain unclear. One key postulates gut-brain axis. There increasing gut microbiota with its proteins, DNA, metabolites influence several processes etiology β-amyloid abnormality, Tau phosphorylation, neuroinflammation. Considering role in AD pathology, this review, we want shed light on bacterial amyloids their potential cerebral amyloid aggregation neuroinflammation provide overview current literature as linker between CD.

Language: Английский

Aβ-oligomers: A potential therapeutic target for Alzheimer's disease DOI
Sudeshna Ghosh, Rafat Ali, Sandeep Verma

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 239, P. 124231 - 124231

Published: March 28, 2023

Language: Английский

Citations

42
Repurposing Antimicrobial Protegrin-1 as a Dual-Function Amyloid Inhibitor via Cross-seeding DOI
Yijing Tang, Dong Zhang, Jie Zheng

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(17), P. 3143 - 3155

Published: Aug. 17, 2023

Amyloids and antimicrobial peptides have traditionally been recognized as distinct families with separate biological functions targets. However, certain amyloids share structural functional characteristics that contribute to the development of neurodegenerative diseases. Specifically, aggregation amyloid-β (Aβ) microbial infections are interconnected pathological factors in Alzheimer's disease (AD). In this study, we propose demonstrate a novel repurposing strategy for an peptide protegrin-1 (PG-1), which exhibits ability simultaneously prevent Aβ infection both vitro vivo. Through comprehensive analysis using protein, cell, worm assays, uncover multiple PG-1 against Aβ, including following: (i) complete inhibition at low molar ratio PG-1/Aβ = 0.25:1, (ii) disassembly preformed fibrils into amorphous aggregates, (iii) reduction Aβ-induced cytotoxicity SH-SY5Y cells transgenic GMC101 nematodes, (iv) preservation original activity P.A., E.coli., S.A., S.E. strains presence Aβ. Mechanistically, dual anti-amyloid anti-bacterial primarily arise from its strong binding seeds (KD 1.24-1.90 μM) through conformationally similar β-sheet associations. This work introduces promising repurpose amyloid inhibitors, effectively targeting pathways AD.

Language: Английский

Citations

9
Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots DOI
Douglas B. Kell, Etheresia Pretorius

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Abstract In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils fibrils exhibiting a cross-β motif parallel or antiparallel β-sheets oriented perpendicular to fibre direction. These can intertwine mature fibres. Similar phenomena occur in blood from individuals circulating inflammatory molecules (also those originating viruses bacteria). presence inflammagens, pathological clotting occur, that results an anomalous termed fibrinaloid microclots. Previous proteomic analyses these microclots have shown non-fibrin(ogen) proteins, suggesting more complex mechanism than simple entrapment. We provide evidence against entrapment model, noting clot pores are too large centrifugation would removed weakly bound proteins. Instead, we explore whether co-aggregation into may involve axial (multiple proteins within same fibril), lateral (single-protein contributing fibre), both types integration. Our analysis data different diseases shows no significant overlap normal plasma proteome correlation between abundance Notably, abundant like α-2-macroglobulin, fibronectin, transthyretin absent microclots, while less such as adiponectin, periostin, von Willebrand Factor well represented. Using bioinformatic tools including AmyloGram AnuPP, found entrapped exhibit high amyloidogenic tendencies, their integration elements structures. This likely contributes microclots’ resistance proteolysis. findings underscore role cross-seeding microclot formation highlight need for further investigation structural properties implications thrombotic diseases. insights foundation developing novel diagnostic therapeutic strategies targeting disorders.

Language: Английский

Citations

2
Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots DOI Open Access
Douglas B. Kell, Etheresia Pretorius

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10809 - 10809

Published: Oct. 8, 2024

In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils fibrils exhibiting a cross-β motif parallel or antiparallel β-sheets oriented perpendicular to fibre direction. These can intertwine mature fibres. Similar phenomena occur in blood from individuals circulating inflammatory molecules (and also some originating viruses bacteria). Such pathological clotting result an anomalous termed fibrinaloid microclots. Previous proteomic analyses these microclots have shown presence non-fibrin(ogen) proteins, suggesting more complex mechanism than simple entrapment. We thus provide evidence against such entrapment model, noting that clot pores are too large centrifugation would removed weakly bound proteins. Instead, we explore whether co-aggregation into may involve axial (multiple proteins within same fibril), lateral (single-protein contributing fibre), both types integration. Our analysis data different diseases shows no significant quantitative overlap normal plasma proteome correlation between abundance their Notably, abundant like α-2-macroglobulin, fibronectin, transthyretin absent microclots, while less as adiponectin, periostin, von Willebrand factor well represented. Using bioinformatic tools, including AmyloGram AnuPP, found entrapped exhibit high amyloidogenic tendencies, integration elements structures. This likely contributes microclots’ resistance proteolysis. findings underscore role cross-seeding microclot formation highlight need for further investigation structural properties implications thrombotic diseases. insights foundation developing novel diagnostic therapeutic strategies targeting disorders.

Language: Английский

Citations

1
Inhibition of Pancreatic Cancer Cells by Different Amyloid Proteins Reveals an Inverse Relationship between Neurodegenerative Diseases and Cancer DOI
Yijing Tang, Dong Zhang,

Sarah Robinson

et al.

Advanced Biology, Journal Year: 2023, Volume and Issue: 7(8)

Published: April 20, 2023

Abstract Neurodegenerative diseases and cancers are considered to be two families of caused by completely opposite cell‐death mechanisms: the former premature cell death, with latter due increased resistance death. Growing epidemiologic evidence appear suggest an inverse correlation between neurodegenerative cancers. However, pathological links, particularly from a protein‐cell interaction perspective, these remains proven. Here, fundamental study investigates effects three amyloid proteins Aβ (associated AD), hIAPP T2D), hCT MTC) on pancreatic cancer (PANC‐1) cells. Collective results demonstrate general inhibitory activity all proliferation, but inhibition efficiencies strongly dependent sequence (Aβ, hIAPP, hCT), concentration (IC25, IC50, IC75), aggregation states (monomers, oligomers). Amyloid exhibit pathways against cells: monomer‐induced ROS production inhibit growth oligomer‐induced membrane disruption kill Collectively, function induce death preventing suppressing migration, promoting reactive oxygen species production, disrupting membranes.

Language: Английский

Citations

3
Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked? DOI Creative Commons
Anna Duda-Madej, Jakub Stecko, Natalia Szymańska

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 8, 2024

Crohn’s disease (CD) is a chronic inflammatory that most frequently affects part of the distal ileum, but it may affect any gastrointestinal tract. CD also be related to systemic inflammation and extraintestinal manifestations. Alzheimer’s (AD) common neurodegenerative disease, gradually worsening behavioral cognitive functions. Despite meaningful progress, both diseases are still incurable have not fully explained, heterogeneous pathomechanism includes immunological, microbiological, genetic, environmental factors. Recently, emerging evidence indicates condition corresponds an increased risk diseases, intestinal inflammation, including CD, increases AD. Even though now known AD, exact pathways connecting these two seemingly unrelated remain unclear. One key postulates gut-brain axis. There increasing gut microbiota with its proteins, DNA, metabolites influence several processes etiology β-amyloid abnormality, Tau phosphorylation, neuroinflammation. Considering role in AD pathology, this review, we want shed light on bacterial amyloids their potential cerebral amyloid aggregation neuroinflammation provide overview current literature as linker between CD.

Language: Английский

Citations

0