Title Tau enhances aggregation of S100A9 protein and further association of its fibrils
Authors Krasauskas, Lukas ; Veiveris, Dominykas ; Žiaunys, Mantas ; Šulskis, Darius ; Sakalauskas, Andrius ; Smirnovas, Vytautas
DOI 10.3390/ijms26188961
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Is Part of International journal of molecular sciences.. Basel : MDPI. 2025, vol. 26, iss. 18, art. no. 8961, p. [1-18].. ISSN 1661-6596. eISSN 1422-0067
Keywords [eng] aggregation ; amyloid ; cross-interaction ; S100A9 ; Tau
Abstract [eng] The formation and accumulation of amyloid fibrils is implicated as one of the main reasons for the onset and progression of several widespread neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Decades of effort to unravel the intricate mechanisms of amyloid aggregation have only led to limited success in developing potent treatment modalities. Generally, this failure is considered to be the result of our incomplete understanding of the processes governing protein transitions into these insoluble fibrillar structures. Recently, a growing number of studies have reported that multiple amyloidogenic proteins, including ones related to the most debilitating disorders, can cross-interact during aggregation. This process leads to different nucleation and fibril elongation rates, aggregate structures, and even their cytotoxicity. Despite this revelation, the entire amyloid interactome remains largely unexplored. In this work, we investigate the cross-interaction between the Alzheimer’s disease-related Tau protein and a pro-inflammatory S100A9 protein, which has recently been implicated as a possible modulator of amyloid aggregation. We show that Tau 2N4R enhances the amyloid aggregation propensity of S100A9 and mediates the self-association of the resulting fibrils, demonstrating this pairing’s potential role in the onset of neurodegenerative disorders.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2025
CC license CC license description