Skip Navigation



Human Molecular Genetics Advance Access published online on September 2, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi331
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
14/20/3003    most recent
ddi331v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Berger, Z.
Right arrow Articles by O'Kane, C. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berger, Z.
Right arrow Articles by O'Kane, C. J
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received July 2, 2005
Revised August 12, 2005
Accepted August 24, 2005

Article

Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway

Zdenek Berger 1, Evangelia K Ttofi 1, Claire H Michel 2, Matthieu Pasco 2, Sean Tenant 2, David C Rubinsztein 3, and Cahir J O'Kane 2*

1 Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK; Department of Genetics, University of Cambridge, CB2 3EH, UK
2 Department of Genetics, University of Cambridge, CB2 3EH, UK
3 Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK

* To whom correspondence should be addressed.
Cahir J O'Kane, E-mail: c.okane{at}gen.cam.ac.uk


  Abstract

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, since 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
S. L. A. Wong, W. M. Chan, and H. Y. E. Chan
Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration
FASEB J, September 1, 2008; 22(9): 3348 - 3357.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. E. Davies, S. Sarkar, and D. C. Rubinsztein
Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation
Hum. Mol. Genet., April 15, 2008; 17(8): 1097 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Sarkar, G. Krishna, S. Imarisio, S. Saiki, C. J. O'Kane, and D. C. Rubinsztein
A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin
Hum. Mol. Genet., January 15, 2008; 17(2): 170 - 178.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. McColl, D. W. Killilea, A. E. Hubbard, M. C. Vantipalli, S. Melov, and G. J. Lithgow
Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans
J. Biol. Chem., January 4, 2008; 283(1): 350 - 357.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
T. Engel, F. Hernandez, J. Avila, and J. J. Lucas
Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3.
J. Neurosci., May 10, 2006; 26(19): 5083 - 5090.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Z. Berger, B. Ravikumar, F. M. Menzies, L. G. Oroz, B. R. Underwood, M. N. Pangalos, I. Schmitt, U. Wullner, B. O. Evert, C. J. O'Kane, et al.
Rapamycin alleviates toxicity of different aggregate-prone proteins
Hum. Mol. Genet., February 1, 2006; 15(3): 433 - 442.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.