* Brazilin Removes Toxic Alpha-Synuclein and Seeding Competent Assemblies from Parkinson Brain by Altering Conformational Equilibrium.
- Alpha-synuclein (α-syn) fibrils, a major constituent of the neurotoxic Lewy Bodies in Parkinson's disease, form via nucleation dependent polymerization and can replicate by a seeding mechanism. Brazilin, a small molecule derived from red cedarwood trees in Brazil, has been shown to inhibit the fibrillogenesis of amyloid-beta (Aβ) and α-syn as well as remodel mature fibrils and reduce cytotoxicity. Here we test the effects of Brazilin on both seeded and unseeded α-syn fibril formation and show that the natural polyphenol inhibits fibrillogenesis of α-syn by a unique mechanism that alters conformational equilibria in two separate points of the assembly mechanism: Brazilin preserves the natively unfolded state of α-syn by specifically binding to the compact conformation of the α-syn monomer. Brazilin also eliminates seeding competence of α-syn assemblies from Parkinson's disease patient brain tissue, and reduces toxicity of pre-formed assemblies in primary neurons by inducing the formation of large fibril clusters. Molecular docking of Brazilin shows the molecule to interact both with unfolded α-syn monomers and with the cross-β sheet structure of α-syn fibrils. Our findings suggest that Brazilin has substantial potential as a neuroprotective and therapeutic agent for Parkinson's disease.
=>〜しようと提案する, を提案する, 示唆する, 暗示する, 提案する
Overview of verb suggest
The verb suggest has 5 senses (first 5 from tagged texts)
1. (57) propose, suggest, advise -- (make a proposal, declare a plan for something; "the senator
proposed to abolish the sales tax")
2. (21) hint, suggest -- (drop a hint; intimate by a hint)
3. (19) suggest, intimate -- (imply as a possibility; "The evidence suggests a need for more
clarification")
4. (14) indicate, suggest -- (suggest the necessity of an intervention; in medicine; "Tetracycline
is indicated in such cases")
5. (12) suggest, evoke, paint a picture -- (call to mind; "this remark evoked sadness")
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