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The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a

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The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a. / Cameron, Amy R.; Wallace, Katherine; Logie, Lisa; Prescott, Alan R.; Unterman, Terry G.; Harthill, Jean; Rena, Graham (Lead / Corresponding author).

In: Biochemical Journal, Vol. 443, No. 1, 01.04.2012, p. 57-64.

Research output: Contribution to journalArticle

Harvard

Cameron, AR, Wallace, K, Logie, L, Prescott, AR, Unterman, TG, Harthill, J & Rena, G 2012, 'The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a' Biochemical Journal, vol 443, no. 1, pp. 57-64., 10.1042/BJ20112124

APA

Cameron, A. R., Wallace, K., Logie, L., Prescott, A. R., Unterman, T. G., Harthill, J., & Rena, G. (2012). The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a. Biochemical Journal, 443(1), 57-64. 10.1042/BJ20112124

Vancouver

Cameron AR, Wallace K, Logie L, Prescott AR, Unterman TG, Harthill J et al. The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a. Biochemical Journal. 2012 Apr 1;443(1):57-64. Available from: 10.1042/BJ20112124

Author

Cameron, Amy R.; Wallace, Katherine; Logie, Lisa; Prescott, Alan R.; Unterman, Terry G.; Harthill, Jean; Rena, Graham (Lead / Corresponding author) / The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a.

In: Biochemical Journal, Vol. 443, No. 1, 01.04.2012, p. 57-64.

Research output: Contribution to journalArticle

Bibtex - Download

@article{4a36ecad90ad44fd8f116ff1c0a8f38f,
title = "The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a",
author = "Cameron, {Amy R.} and Katherine Wallace and Lisa Logie and Prescott, {Alan R.} and Unterman, {Terry G.} and Jean Harthill and Graham Rena",
year = "2012",
doi = "10.1042/BJ20112124",
volume = "443",
number = "1",
pages = "57--64",
journal = "Biochemical Journal",
issn = "0264-6021",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The anti-neurodegenerative agent clioquinol regulates the transcription factor FOXO1a

A1 - Cameron,Amy R.

A1 - Wallace,Katherine

A1 - Logie,Lisa

A1 - Prescott,Alan R.

A1 - Unterman,Terry G.

A1 - Harthill,Jean

A1 - Rena,Graham

AU - Cameron,Amy R.

AU - Wallace,Katherine

AU - Logie,Lisa

AU - Prescott,Alan R.

AU - Unterman,Terry G.

AU - Harthill,Jean

AU - Rena,Graham

PY - 2012/4/1

Y1 - 2012/4/1

N2 - <p>Many diseases of aging including AD (Alzheimer's disease) and T2D (Type 2 diabetes) are strongly associated with common risk factors, suggesting that there may be shared aging mechanisms underlying these diseases, with the scope to identify common cellular targets for therapy. In the present study we have examined the insulin-like signalling properties of an experimental AD 8-hydroxyquinoline drug known as CQ (clioquinol). The IIS [insulin/IGF-1 (insulin-like growth factor-1) signalling] kinase Akt/PKB (protein kinase B) inhibits the transcription factor FOXO1a (forkhead box O1a) by phosphorylating it on residues that trigger its exit from the nucleus. In HEK (human embryonic kidney)-293 cells, we found that CQ treatment induces similar responses. A key transcriptional response to US is the inhibition of hepatic gluconeogenic gene expression, and, in rat liver cells, CQ represses expression of the key gluconeogenic regulatory enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). The effects on FOXO1. a and gluconeogenic gene expression require the presence of Zn2+ ions, reminiscent of much earlier studies examining diabetogenic properties of 8-hydroxyquinolines. Comparative investigation of the signalling properties of a panel of these compounds demonstrates that CQ alone exhibits FOXO1a regulation without diabetogenicity. Our results suggest that Zn2+-dependent regulation of FOXOs and gluconeogenesis may contribute to the therapeutic properties of this drug. Further investigation of this signalling response might illuminate novel pharmacological strategies for the treatment of age-related diseases.</p>

AB - <p>Many diseases of aging including AD (Alzheimer's disease) and T2D (Type 2 diabetes) are strongly associated with common risk factors, suggesting that there may be shared aging mechanisms underlying these diseases, with the scope to identify common cellular targets for therapy. In the present study we have examined the insulin-like signalling properties of an experimental AD 8-hydroxyquinoline drug known as CQ (clioquinol). The IIS [insulin/IGF-1 (insulin-like growth factor-1) signalling] kinase Akt/PKB (protein kinase B) inhibits the transcription factor FOXO1a (forkhead box O1a) by phosphorylating it on residues that trigger its exit from the nucleus. In HEK (human embryonic kidney)-293 cells, we found that CQ treatment induces similar responses. A key transcriptional response to US is the inhibition of hepatic gluconeogenic gene expression, and, in rat liver cells, CQ represses expression of the key gluconeogenic regulatory enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). The effects on FOXO1. a and gluconeogenic gene expression require the presence of Zn2+ ions, reminiscent of much earlier studies examining diabetogenic properties of 8-hydroxyquinolines. Comparative investigation of the signalling properties of a panel of these compounds demonstrates that CQ alone exhibits FOXO1a regulation without diabetogenicity. Our results suggest that Zn2+-dependent regulation of FOXOs and gluconeogenesis may contribute to the therapeutic properties of this drug. Further investigation of this signalling response might illuminate novel pharmacological strategies for the treatment of age-related diseases.</p>

UR - http://www.scopus.com/inward/record.url?scp=84858307296&partnerID=8YFLogxK

U2 - 10.1042/BJ20112124

DO - 10.1042/BJ20112124

M1 - Article

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

VL - 443

SP - 57

EP - 64

ER -

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