Structural Characteristics of α-Synuclein Oligomers Stabilized by the Flavonoid Baicalein
作者： Dong-Pyo Hong , Anthony L. Fink , Vladimir N. Uversky
DOI: 10.1016/J.JMB.2008.08.039
关键词: Biochemistry 、 Chemistry 、 Alpha-synuclein 、 Oligomer 、 Membrane permeability 、 Fibril 、 Circular dichroism 、 Membrane lipids 、 Monomer 、 Baicalein
摘要: The flavonoid baicalein inhibits fibrillation of α-synuclein, which is a major component the Lewy bodies in Parkinson’s disease. It has been known that induces formation α-synuclein oligomers and consequently prevents its fibrillation. In order to evaluate structural properties baicalein-stabilized oligomers, we purified oligomer species by HPLC examined their stability structure CD, FTIR, SEC-HPLC, SAXS, AFM. Baicalein-stabilized are β-sheet-enriched according CD FTIR analysis. They did not form fibrils even after very prolonged incubation. From SAXS data AFM images, were characterized as quite compact globular species. Oligomers extremely stable, with GdmCl Cm=3.3 M. This high explains previously observed inhibition toward These being added solution aggregating able noticeably inhibit After co-incubation, short formed, suggesting effective interaction monomeric α-synuclein. Membrane permeability tests suggested had mild effect on integrity membrane surface. was rather similar protein, targeted stabilization certain might offer potential strategy for development novel disease therapies.
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sci-hub.se 参考文章(40)
Chun-Ching Lin, Den-En Shieh, Li-Teh Liu, Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Research. ,vol. 20, pp. 2861- 2865 ,(2000)
K. A. Conway, Kinetic Stabilization of the alpha -Synuclein Protofibril by a Dopamine-alpha -Synuclein Adduct Science. ,vol. 294, pp. 1346- 1349 ,(2001) , 10.1126/SCIENCE.1063522
Maria Grazia Spillantini, Marie Luise Schmidt, Virginia M.-Y. Lee, John Q. Trojanowski, Ross Jakes, Michel Goedert, α-Synuclein in Lewy bodies Nature. ,vol. 388, pp. 839- 840 ,(1997) , 10.1038/42166
Lennart Mucke, Eliezer Masliah, Gui-Qiu Yu, Margaret Mallory, Edward M. Rockenstein, Gwen Tatsuno, Kang Hu, Dora Kholodenko, Kelly Johnson-Wood, Lisa McConlogue, High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. The Journal of Neuroscience. ,vol. 20, pp. 4050- 4058 ,(2000) , 10.1523/JNEUROSCI.20-11-04050.2000
Nadia Benaroudj, Alfred L. Goldberg, PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone. Nature Cell Biology. ,vol. 2, pp. 833- 839 ,(2000) , 10.1038/35041081
Glatter O, Kratky O, Pilz I, Small Angle X-Ray Scattering ,(1982)
Dean M. Hartley, Dominic M. Walsh, Chianping P. Ye, Thekla Diehl, Sara Vasquez, Peter M. Vassilev, David B. Teplow, Dennis. J. Selkoe, Protofibrillar Intermediates of Amyloid β-Protein Induce Acute Electrophysiological Changes and Progressive Neurotoxicity in Cortical Neurons The Journal of Neuroscience. ,vol. 19, pp. 8876- 8884 ,(1999) , 10.1523/JNEUROSCI.19-20-08876.1999
Jie Li, Min Zhu, Amy B. Manning-Bog, Donato A. Di Monte, Anthony L. Fink, Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease The FASEB Journal. ,vol. 18, pp. 962- 964 ,(2004) , 10.1096/FJ.03-0770FJE
Bao Qun Li, Tao Fu, Wang-Hua Gong, Nancy Dunlop, Hsiang-fu Kung, Yaodong Yan, Jian Kang, Ji Ming Wang, The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines Immunopharmacology. ,vol. 49, pp. 295- 306 ,(2000) , 10.1016/S0162-3109(00)00244-7
Takayuki Ikezoe, Sophie S. Chen, David Heber, Hirokuni Taguchi, H. Phillip Koeffler, BAICALIN IS A MAJOR COMPONENT OF PC-SPES WHICH INHIBITS THE PROLIFERATION OF HUMAN CANCER CELLS VIA APOPTOSIS AND CELL CYCLE ARREST The Prostate. ,vol. 49, pp. 285- 292 ,(2001) , 10.1002/PROS.10024