Journal
HUMAN MOLECULAR GENETICS
Volume 14, Issue 20, Pages 3003-3011Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddi331
Keywords
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Funding
- Medical Research Council [G0000872] Funding Source: Medline
- MRC [G0000872] Funding Source: UKRI
- Medical Research Council [G0000872] Funding Source: researchfish
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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 GSK3 beta-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.
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