Localized changes to glycogen synthase kinase-3 and collapsin response mediator protein-2 in the Huntington's disease affected brain

NKH Lim; LW Hung; TY Pang; CA Mclean; JR Liddell; JB Hilton; QX Li; AR White; AJ Hannan; PJ Crouch

Journal article

Localized changes to glycogen synthase kinase-3 and collapsin response mediator protein-2 in the Huntington's disease affected brain

NKH Lim, LW Hung, TY Pang, CA Mclean, JR Liddell, JB Hilton, QX Li, AR White, AJ Hannan, PJ Crouch

Human Molecular Genetics | Published : 2014

DOI: 10.1093/hmg/ddu119

Abstract

All cases of Huntington's disease (HD) are caused by mutant huntingtin protein (mhtt), yet the molecular mechanisms that link mhtt to disease symptoms are not fully elucidated. Given glycogen synthase kinase-3 (GSK3) is implicated in several neurodegenerative diseases as a molecular mediator of neuronal decline and widely touted as a therapeutic target, we investigated GSK3 in cells expressing mhtt, brains of R6/1 HD mice and post-mortem human brain samples. Consistency in data across the two models and the human brain samples indicate decreased GSK3 signalling contributes to neuronal dysfunction in HD. Inhibitory phosphorylation of GSK3 (pGSK3) was elevated in mhtt cells and this appeared r..

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University of Melbourne Researchers

Catriona McLean Author

Jeffrey Liddell Author

James Hilton Author

Qiao-Xin Li Author

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Grants

Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

This work was supported by the Australian National Health and Medical Research Council (1005651 to P.J.C. and Q. X. L., 509031 to A.J.H.); The University of Melbourne (C. R. Roper Fellowship to P.J.C.); and the Australian Research Council (Future Fellowships to A.J.H. and A.R.W.).