Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity. Export

@article{citeulike:1943736, abstract = {Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract within the huntingtin protein (Htt). Identifying the pathways that are altered in response to the mutant protein is crucial for understanding the cellular processes impacted by the disease as well as for the rational development of effective pharmacological interventions. Here, expression profiling of a cellular HD model identifies genes that implicate altered mitogen-activated protein kinase (MAPK) signaling. Targeted biochemical studies and pharmacological modulation of these MAPK pathways suggest that mutant Htt affects signaling at upstream points such that both ERK and JNK are activated. Modulation of the ERK pathway suggests that this pathway is associated with cell survival, whereas inhibition of JNK was found to effectively suppress pathogenesis. These studies suggest that pharmacological intervention in MAPK pathways, particularly at the level of ERK activation, may be an appropriate approach to HD therapy.}, address = {Department of Psychiatry and Human Behavior, University of California, Irvine, 92697, USA.}, author = {Apostol, B. L. and Illes, K. and Pallos, J. and Bodai, L. and Wu, J. and Strand, A. and Schweitzer, E. S. and Olson, J. M. and Kazantsev, A. and Marsh, J. L. and Thompson, L. M.}, citeulike-article-id = {1943736}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/16330479}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=16330479}, day = {15}, issn = {0964-6906}, journal = {Hum Mol Genet}, keywords = {huntington, microarray}, month = {January}, number = {2}, pages = {273--285}, posted-at = {2007-11-20 15:40:24}, priority = {2}, title = {Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16330479}, volume = {15}, year = {2006} }

TY - JOUR ID - citeulike:1943736 L3 - citeulike-article-id:1943736 N2 - Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract within the huntingtin protein (Htt). Identifying the pathways that are altered in response to the mutant protein is crucial for understanding the cellular processes impacted by the disease as well as for the rational development of effective pharmacological interventions. Here, expression profiling of a cellular HD model identifies genes that implicate altered mitogen-activated protein kinase (MAPK) signaling. Targeted biochemical studies and pharmacological modulation of these MAPK pathways suggest that mutant Htt affects signaling at upstream points such that both ERK and JNK are activated. Modulation of the ERK pathway suggests that this pathway is associated with cell survival, whereas inhibition of JNK was found to effectively suppress pathogenesis. These studies suggest that pharmacological intervention in MAPK pathways, particularly at the level of ERK activation, may be an appropriate approach to HD therapy. IS - 2 JF - Hum Mol Genet SN - 0964-6906 AD - Department of Psychiatry and Human Behavior, University of California, Irvine, 92697, USA. EP - 285 TI - Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity. VL - 15 SP - 273 KW - huntington KW - microarray AU - Apostol, BL AU - Illes, K AU - Pallos, J AU - Bodai, L AU - Wu, J AU - Strand, A AU - Schweitzer, ES AU - Olson, JM AU - Kazantsev, A AU - Marsh, JL AU - Thompson, LM PY - 2006/01/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/16330479 ER -