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Article: Baicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aβ peptide fibrillation and oligomerisation

TitleBaicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aβ peptide fibrillation and oligomerisation
Authors
Issue Date2011
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.chembiochem.com
Citation
Chembiochem, 2011, v. 12 n. 4, p. 615-624 How to Cite?
AbstractAbnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-β peptide (Aβ) aggregation and toxicity. We found that baicalein can also inhibit Aβ fibrillation and oligomerisation, disaggregate pre-formed Aβ amyloid fibrils and prevent Aβ fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders. Arrested aggregation: Baicalein, a flavonoid from the Chinese herbal medicine Scutellaria baicalensis Georgi, is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also a effective inhibitor of α-syn fibrillation in cell-free systems. It inhibits the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protects SH-SY5Y cells from α-syn-oligomer-induced toxicity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Persistent Identifierhttp://hdl.handle.net/10722/147627
ISSN
2015 Impact Factor: 2.85
2015 SCImago Journal Rankings: 1.301
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Baptist UniversityFRG-II/09-10/051
Eu Yan Sang (Hong Kong) LimitedEYS/07-08/01
Lions Club of South Kowloon, H.K.
Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences (Dubai, UAE)MRG-23/2005-2006
UAE University (Al Ain, UAE)01-03-8-12/08
Funding Information:

GNS and SGC plasmids were generous gifts from Dr. Pamela J. McLean, Harvard University, USA. NU1 antibody was donated by Dr. William L. Klein, Northwestern University, USA. 10G4 antibody was donated by Drs. Fusheng Yang and Greg Cole, University of California, USA. The study was supported by research grant FRG-II/09-10/051 from Hong Kong Baptist University, and also it was partly supported by grant EYS/07-08/01 from Eu Yan Sang (Hong Kong) Limited. We especially thank Pui-Chun Lam, Wai-Sheung Chan and the Lions Club of South Kowloon, H.K. for their further financial support of this study. The laboratory of O.M.E. is supported by Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences (Dubai, UAE; Grant MRG-23/2005-2006), and UAE University (Al Ain, UAE; Interdisciplinary Research Project 01-03-8-12/08). We would also like to thank Dr. Martha Dahlen for her critical review and revision.

References

 

DC FieldValueLanguage
dc.contributor.authorLu, JHen_US
dc.contributor.authorArdah, MTen_US
dc.contributor.authorDurairajan, SSKen_US
dc.contributor.authorLiu, LFen_US
dc.contributor.authorXie, LXen_US
dc.contributor.authorFong, WFDen_US
dc.contributor.authorHasan, MYen_US
dc.contributor.authorHuang, JDen_US
dc.contributor.authorElAgnaf, OMAen_US
dc.contributor.authorLi, Men_US
dc.date.accessioned2012-05-29T06:05:04Z-
dc.date.available2012-05-29T06:05:04Z-
dc.date.issued2011en_US
dc.identifier.citationChembiochem, 2011, v. 12 n. 4, p. 615-624en_US
dc.identifier.issn1439-4227en_US
dc.identifier.urihttp://hdl.handle.net/10722/147627-
dc.description.abstractAbnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-β peptide (Aβ) aggregation and toxicity. We found that baicalein can also inhibit Aβ fibrillation and oligomerisation, disaggregate pre-formed Aβ amyloid fibrils and prevent Aβ fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders. Arrested aggregation: Baicalein, a flavonoid from the Chinese herbal medicine Scutellaria baicalensis Georgi, is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also a effective inhibitor of α-syn fibrillation in cell-free systems. It inhibits the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protects SH-SY5Y cells from α-syn-oligomer-induced toxicity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.en_US
dc.languageengen_US
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.chembiochem.comen_US
dc.relation.ispartofChemBioChemen_US
dc.subject.meshAmyloid - Biosynthesisen_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDrugs, Chinese Herbal - Chemistry - Pharmacologyen_US
dc.subject.meshEnzyme Inhibitors - Chemistry - Pharmacologyen_US
dc.subject.meshFlavanones - Chemistry - Pharmacologyen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshAlpha-Synuclein - Antagonists & Inhibitors - Chemistryen_US
dc.titleBaicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aβ peptide fibrillation and oligomerisationen_US
dc.typeArticleen_US
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_US
dc.identifier.authorityHuang, JD=rp00451en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/cbic.201000604en_US
dc.identifier.pmid21271629-
dc.identifier.scopuseid_2-s2.0-79952010449en_US
dc.identifier.hkuros192259-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952010449&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12en_US
dc.identifier.issue4en_US
dc.identifier.spage615en_US
dc.identifier.epage624en_US
dc.identifier.isiWOS:000288080700017-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridLu, JH=16175647100en_US
dc.identifier.scopusauthoridArdah, MT=36668287000en_US
dc.identifier.scopusauthoridDurairajan, SSK=23469201000en_US
dc.identifier.scopusauthoridLiu, LF=40561366800en_US
dc.identifier.scopusauthoridXie, LX=23483050700en_US
dc.identifier.scopusauthoridFong, WFD=36833162500en_US
dc.identifier.scopusauthoridHasan, MY=55057475100en_US
dc.identifier.scopusauthoridHuang, JD=8108660600en_US
dc.identifier.scopusauthoridElAgnaf, OMA=7003671192en_US
dc.identifier.scopusauthoridLi, M=36071647500en_US

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