Effects of mutant huntingtin on mGluR5-mediated dual signaling pathways: implications for therapeutic interventions.

Cellular and Molecular Neurobiology
Shan-Shan HuangHe Li

Abstract

Glutamate excitotoxicity is thought to play an important role in Huntington's disease (HD), which is caused by a polyglutamine expansion in the HD protein huntingtin (htt). Overactivation of group I metabotropic glutamate receptors (mGluRs), which include mGluR1 as well as mGluR5 and are coupled via phospholipase C to the inositol phosphate pathway, is found to be involved in mutant htt-mediated neurotoxicity. However, activation of mGluR5 also leads to neuronal protection. Here, we report that mutant htt can activate both mGluR5-mediated ERK and JNK signaling pathways. While increased JNK signaling causes cell death, activation of ERK signaling pathway is protective against cell death. Expression of mutant htt in cultured cells causes greater activation of JNK than ERK. These findings suggest that selective inhibition of the JNK signaling pathway may offer an effective therapeutic approach for reducing htt-mediated excitotoxicity.

References

Jul 1, 1990·Trends in Neurosciences·M DiFiglia
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·P J Conn, J P Pin
Jul 1, 1997·Brain Pathology·M A Nance
May 22, 1998·Journal of Neuropathology and Experimental Neurology·J P Vonsattel, M DiFiglia
Apr 27, 1999·Journal of Neurochemistry·N ChenL A Raymond
Jun 30, 2001·Trends in Pharmacological Sciences·M J Marinissen, J S Gutkind
Oct 20, 2001·Molecular Neurobiology·K NozakiN Hashimoto
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·B L BennettD W Anderson
Dec 4, 2001·Biology of the Cell·V Volmat, J Pouysségur
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·Kathleen A Gallo, Gary L Johnson
Oct 28, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Luca Colucci-D'AmatoUmberto di Porzio
May 22, 2004·European Journal of Biochemistry·Charleen T ChuDonald B DeFranco
Sep 1, 2004·Biochemical and Biophysical Research Communications·Ilya Bezprozvanny, Michael R Hayden
Sep 24, 2004·Science's STKE : Signal Transduction Knowledge Environment·Eric C C Cheung, Ruth S Slack
Feb 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Tie-Shan TangIlya Bezprozvanny
Aug 11, 2005·The Journal of Biological Chemistry·Pieter H AnborghStephen S G Ferguson
Jan 20, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lu YangJohn Q Wang
Feb 18, 2006·Journal of Neuroscience Methods·Raeann L CarrierKari R Hoyt
Apr 26, 2008·Investigative Ophthalmology & Visual Science·Yuan LeiJames E Morgan
Aug 7, 2009·Clinical and Experimental Pharmacology & Physiology·Adam CollisonJoerg Mattes

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Citations

Feb 16, 2012·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·László Bodai, J Lawrence Marsh
May 20, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Fang FangHe Li
Apr 26, 2017·International Journal of Molecular Medicine·Jing Sun, Guangxian Nan

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