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Brazilin Inhibits α-Synuclein Fibrillogenesis, Disrupts Mature Fibrils, and Protects Against Amyloid-Induced Cytotoxicity

Brazilin Inhibits α-Synuclein Fibrillogenesis, Disrupts Mature Fibrils, and Protects Against Amyloid-Induced Cytotoxicity

Fufeng Liu, Ying Wang, Jingcheng Sang, Wei Wei, Wenping Zhao, Beibei Chen, Fang Zhao, Longgang Jia, Fuping Lu

J Agric Food Chem. 2019 Oct 23;67(42):11769-11777.

PMID: 31575115

Abstract:

The inhibitory effect of brazilin against α-synuclein (α-syn) fibrillogenesis, disruption effect against mature fibrils, and the following cytotoxicity were examined by systematical biochemical, biophysical, cellular biological, and molecular simulation experiments. It is found that brazilin inhibited α-syn fibrillogenesis and disrupted the performed fibrils with a concentration-dependent manner. Moreover, cellular experimental data showed that brazilin effectively reduced the cytotoxicity induced by α-syn aggregates. Finally, molecular dynamics simulations were performed to explore the interactions between brazilin and α-syn pentamer. It is found that brazilin directly interacts with α-syn pentamer, and the hydrophobic interactions are favorable for brazilin binding with the α-syn pentamer, while the electrostatic part provides adverse effects. Three binding regions were identified to inhibit α-syn fibrillogenesis or disrupt the preformed aggregates. Furthermore, six important residues (i.e., G51, V52, A53, E61, V66, and K80) of α-syn were also identified. We expected that brazilin is an effective agent against α-syn fibrillogenesis and associated cytotoxicity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP474077-A	Brazilin		474-07-7	Price

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