Brazilin inhibits α-synuclein fibrillogenesis, disrupts mature fibrils and protects against amyloid-induced cytotoxicity
2019
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’s found that brazilin directly interacts with α-syn pentamer. And, the hydrophobic interactions are favorable for brazilin binding with the α-syn pentamer, while electrostatic part provides adverse effect. 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...
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