Epigallocatechin-3-Gallate: A potential amyloid Fibril Disaggregator of Serum amyloid A1.

Abstract

Serum amyloid A1 (SAA1) is a 122-amino acid protein that, after cleavage, matures into a 104-amino acid form. Its N-terminus is responsible for binding high-density lipoprotein (HDL), while the C-terminus maintains its structural integrity. As an acute-phase protein, SAA1 is produced by the liver in response to acute inflammation. SAA1 is also a precursor to amyloid A (AA), and its accumulation can lead to AA amyloidosis-a condition secondary to chronic inflammation that causes tissue damage and organ dysfunction. Our study explores methods to disaggregate SAA1 fibrils isolated from the cat spleen, chicken liver, and cow liver. Specifically, we investigate the use of epigallocatechin-3-gallate (EGCG), a polyphenolic flavonoid extracted from green tea known for its anti-inflammatory and antioxidant properties, to disaggregate these fibrils. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to analyze these fibrils after treatment with 1 % DMSO and 400 μM of EGCG in 10 mM PBS (pH 7.4). The results demonstrated that EGCG effectively reduced fibril size, as confirmed by DLS characterization, with the disappearance or diminished prominence of the 10^3-4 nm peak. Additional TEM results confirmed that EGCG disaggregated amyloid-beta fibrils isolated from Alzheimer's disease brains. These findings suggest that compounds like EGCG could be valuable in treating inflammatory and neurodegenerative conditions by disaggregating amyloid fibrils.