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Antimicrobial, polarizing light, and paired helical filament properties of fragmented tau peptides of selected putative gingipains

Kanagasingam, Shalini, von Ruhland, Christopher, Welbury, Richard and Singhrao, Sim K. 2022. Antimicrobial, polarizing light, and paired helical filament properties of fragmented tau peptides of selected putative gingipains. Journal of Alzheimer's Disease 89 (4) 10.3233/JAD-220486

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Abstract

Background:Tau is an established substrate for gingipains secreted by Porphyromonas gingivalis. Hyperphosphorylation of tau and neurofibrillary tangle (NFT) formation is a defining lesion of Alzheimer’s disease (AD) where NFT distribution is related to Braak stage and disease severity. Objective:To assess gingipains’-fragmented tau peptides for their antimicrobial properties and for the likelihood of paired helical/straight filament (PHF/SF) formation with implications for the NFT lesion. Methods:Seven non-phosphorylated (A-G) and three phosphorylated (A-C) tau peptides, were tested for antimicrobial properties against P. gingivalis. Polarizing light properties were determined using Congo Red staining. Secondary and tertiary structures of peptides B-F were determined using transmission electron microscopy (TEM) and circular dichroism (CD) was undertaken for the soluble peptides A in phosphorylated and non-phosphorylated states. Results:Phosphorylated tau peptide A displayed a significant effect against planktonic P. gingivalis. The CD results demonstrated that both peptides A, in phosphorylated and non-phosphorylated states, in aqueous solution, adopted mainly β-type structures. Non-phosphorylated peptides B-F and phosphorylated peptides B-C were insoluble and fibrillar under the TEM. The secondary and tertiary structures of the non-phosphorylated peptide B demonstrated fewer helical twists, whereas peptide C displayed significantly more helical twists along the whole fiber(s) length following its phosphorylation. Conclusion:Phosphorylated peptide A reduced P. gingivalis viability. CD spectroscopy demonstrated the phosphorylated and the non-phosphorylated peptide A predominantly formed from β-sheet structures in aqueous solution with potential antimicrobial activity. Phosphorylation of tau peptides physically changed their tertiary structure into PHFs with potential for self-aggregation and binding to the NFT lesion.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: IOS Press
ISSN: 1387-2877
Date of First Compliant Deposit: 11 November 2022
Date of Acceptance: 25 July 2022
Last Modified: 03 May 2023 11:30
URI: https://orca.cardiff.ac.uk/id/eprint/154130

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