Journal Article

Lithium rescues toxicity of aggregate-prone proteins in <i>Drosophila</i> by perturbing Wnt pathway

Zdenek Berger, Evangelia K. Ttofi, Claire H. Michel, Matthieu Y. Pasco, Sean Tenant, David C. Rubinsztein and Cahir J. O'Kane

in Human Molecular Genetics

Volume 14, issue 20, pages 3003-3011
Published in print October 2005 | ISSN: 0964-6906
Published online September 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi331
Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway

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We have previously shown that lithium can protect against the polyglutamine toxicity of the Huntington's disease mutation in cell models. Here, we demonstrate for the first time in vivo that lithium can protect against the toxicity caused by aggregate-prone proteins with either polyglutamine or polyalanine expansions in Drosophila. We also show that these protective effects can be partly accounted for by lithium acting through the Wnt/Wg pathway, as a GSK3β-specific inhibitor and overexpression of dTCF also mediate protective effects. Our data suggest that lithium deserves serious consideration for further studies as a therapeutic for polyglutamine diseases, particularly as it is an established drug that has been used for several decades for chronic treatment of affective disorders.

Journal Article.  6415 words.  Illustrated.

Subjects: Genetics and Genomics

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