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Tannic Acid Inhibits α-Synuclein Amyloid Fibril Formation via Binding to the Monomer N-terminal Domain

Stoeber, J.; Williams, J. K.; Moghe, P. V.; Baum, J.

2021-05-26 biochemistry
10.1101/2021.05.26.445860 bioRxiv
Show abstract

-Synuclein (S) is an intrinsically disordered protein (IDP) that aggregates into amyloid fibrils during the progression of Parkinsons Disease and other synucleinopathies. The N-terminal domain (residues 1-60) is now understood to play a critical role in the initial nucleation of aggregation, as well as a pivotal role in the monomer-fibril interaction underlying amyloid seeding. Here we report on the interaction between S and the polyphenol tannic acid (TA), where a combination of solution NMR, atomic force microscopy (AFM), and ThT assays have identified that TA targets the S N-terminal domain to inhibit amyloid fibril formation in a pH dependent manner. This work highlights the importance of targeting the N-terminus of S to arrest fibril formation, and suggests the importance of including polyphenolic moieties in future amyloid inhibitors.

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