Naringenin as a potent anti-amyloidogenic polyphenol against a-synuclein aggregation: a computational approach

Misfolding and aggregation of the protein alpha-synuclein (a-syn) triggers Parkinson's disease PD. Amyloid aggregates, typically rich in β-sheets, are prime targets for reducing their neurotoxic effects. Various literatures reported that administration of small molecule inhibitors derived from polyphenolic flavonoid compounds could be considered as a potential therapeutic approach against neurological disorders. Hence, we have identified a promising flavonoid compound through molecular docking and molecular dynamics (MD) simulations that effectively inhibits the amyloidogenic behavior of a-syn. Initial screening of flavonoids identified Epicatechin, Naringenin, and Silymarin as promising drug leads. The Naringenin-a-syn complex showed significant binding and higher residual energy contribution than other flavonoid compounds. The results showed that Naringenin reduces the abundance of β-sheets and changes in structural stability, hydrophobicity and protein flexibility compared to other flavonoid compounds. Hence, Naringenin could be a productive therapeutic candidate to efficiently ameliorate aberrant a-syn amyloid-mediated neurotoxicity, eventually attenuating the nocuous effects of PD.