Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide

Raman, Bakthisaran; Ban, Tadato; Yamaguchi, Kei-ichi; Sakai, Miyo; Kawai, Tomoji; Naiki, Hironobu; Goto, Yuji

doi:https://doi.org/10.1074/jbc.M500309200

Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide

Raman, Bakthisaran; Ban, Tadato; Yamaguchi, Kei-ichi et al.

Journal of Biological Chemistry, 2005, 280(16), 16157-16162

Number of Access:853（2025-12-07 00:00 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71294

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Title	Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide
Creator	CreatorName Raman, Bakthisaran
	NRID 1000000579667 1000000579667 CreatorName Ban, Tadato
	NRID 1000090432187 1000090432187 researchmap permalink read0105908 read0105908 Scopus Author ID 8731908100 8731908100 CreatorName Yamaguchi, Kei-ichi
	CreatorName Sakai, Miyo
	NRID 1000020092546 1000020092546 CreatorName Kawai, Tomoji
	NRID 1000010227704 1000010227704 CreatorName Naiki, Hironobu
	NRID 1000040153770 1000040153770 researchmap permalink read0014440 read0014440 CreatorName Goto, Yuji
Description	This research was originally published in the Journal of Biological Chemistry. Bakthisaran Raman, Tadato Ban, Kei-ichi Yamaguchi, Miyo Sakai, Tomoji Kawai, Hironobu Naiki and Yuji Goto. Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide. J. Biol. Chem. 2005; 280, 16157-16162. © the American Society for Biochemistry and Molecular Biology
Abstract	Although metal ions such as Cu2+, Zn2+, and Fe3+ are implicated to play a key role in Alzheimer disease, their role is rather complex, and comprehensive understanding is not yet obtained. We show that Cu2+ and Zn2+ but not Fe3+ renders the amyloid β peptide, Aβ1–40, nonfibrillogenic in nature. However, preformed fibrils of Aβ1–40 were stable when treated with these metal ions. Consequently, fibril growth of Aβ1–40 could be switched on/off by switching the molecule between its apo- and holo-forms. Clioquinol, a potential drug for Alzheimer disease, induced resumption of the Cu2+-suppressed but not the Zn2+-suppressed fibril growth of Aβ1–40. The observed synergistic effect of clioquinol and Zn2+ suggests that Zn2+-clioquinol complex effectively retards fibril growth. Thus, clioquinol has dual effects; although it disaggregates the metal ion-induced aggregates of Aβ1–40 through metal chelation, it further retards the fibril growth along with Zn2+. These results indicate the mechanism of metal ions in suppressing Aβ amyloid formation, as well as providing information toward the use of metal ion chelators, particularly clioquinol, as potential drugs for Alzheimer disease.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	280(16)
Page	16157-16162
Date of Issued	2005-04
Language	English
Handle URL	https://hdl.handle.net/11094/71294
eISSN	1083351X
NCID	AA1202463X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M500309200
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2005, 280(16), p. 16157-16162
DC.title	Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide
DC.creator	Raman, Bakthisaran
	Ban, Tadato
	Yamaguchi, Kei-ichi
	Sakai, Miyo
	Kawai, Tomoji
	Naiki, Hironobu
	Goto, Yuji
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2005-04
DC.identifier	https://doi.org/10.1074/jbc.M500309200
DC.description	This research was originally published in the Journal of Biological Chemistry. Bakthisaran Raman, Tadato Ban, Kei-ichi Yamaguchi, Miyo Sakai, Tomoji Kawai, Hironobu Naiki and Yuji Goto. Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide. J. Biol. Chem. 2005; 280, 16157-16162. © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	Although metal ions such as Cu2+, Zn2+, and Fe3+ are implicated to play a key role in Alzheimer disease, their role is rather complex, and comprehensive understanding is not yet obtained. We show that Cu2+ and Zn2+ but not Fe3+ renders the amyloid β peptide, Aβ1–40, nonfibrillogenic in nature. However, preformed fibrils of Aβ1–40 were stable when treated with these metal ions. Consequently, fibril growth of Aβ1–40 could be switched on/off by switching the molecule between its apo- and holo-forms. Clioquinol, a potential drug for Alzheimer disease, induced resumption of the Cu2+-suppressed but not the Zn2+-suppressed fibril growth of Aβ1–40. The observed synergistic effect of clioquinol and Zn2+ suggests that Zn2+-clioquinol complex effectively retards fibril growth. Thus, clioquinol has dual effects; although it disaggregates the metal ion-induced aggregates of Aβ1–40 through metal chelation, it further retards the fibril growth along with Zn2+. These results indicate the mechanism of metal ions in suppressing Aβ amyloid formation, as well as providing information toward the use of metal ion chelators, particularly clioquinol, as potential drugs for Alzheimer disease.
DC.format	71294
citation_title	Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide
citation_author	Raman, Bakthisaran
	Ban, Tadato
	Yamaguchi, Kei-ichi
	Sakai, Miyo
	Kawai, Tomoji
	Naiki, Hironobu
	Goto, Yuji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2005-04
citation_journal_title	Journal of Biological Chemistry
citation_volume	280
citation_issue	16
citation_firstpage	16157
citation_lastpage	16162
citation_doi	https://doi.org/10.1074/jbc.M500309200
citation_public_url	https://hdl.handle.net/11094/71294

Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide

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