| Title | Molecular mechanisms underlying the flavonoid-induced inhibition of -synuclein fibrillation. | | Author(s) | Meng X, Munishkina LA, Fink AL, Uversky VN | | Source | Biochemistry 2009 Jul 27. | | Abstract | The molecular mechanism underlying the flavonoid-induced inhibition of alpha-synuclein fibrillation was thoroughly examined by various biochemical and biophysical approaches. The noncovalent binding of the inhibitory flavonoids to alpha-synuclein and the covalent modification by the flavonoid quinone led to the restriction of the conformational changes in this natively unfolded protein and to the stabilization of soluble flavonoid-modified species of alpha-synuclein (monomers and oligomers). All of these factors rather than a single one contribute to the inhibition of WT alpha-synuclein fibrillation induced by the flavonoid. The structural requirements that appear necessary to provide a flavonoid the ability to inhibit alpha-synuclein fibrillation were determined to be vicinal dihydroxyphenyl moieties, irrespectively the ring position they are located. Flavonoids with three vicinal hydroxyl groups exhibited enhanced inhibitory effects on alpha-synuclein fibrillation. The antioxidant activities of flavonoids were generally correlated with their in vitro inhibitory effects on alpha-synuclein fibrillation. The flavonoids inhibiting alpha-synuclein fibrillation and stabilizing the protein monomeric conformation can serve as a model for the development of therapeutic drugs in combating Parkinson's disease. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19634918 |
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