title: JNK: A Putative Link Between Insulin Signaling and VGLUT1 in Alzheimer's Disease.
abstract: In the present work, the involvement of JNK in insulin signaling alterations and its role in glutamatergic deficits in Alzheimer's disease (AD) has been studied. In postmortem cortical tissues, pJNK levels were increased, while insulin signaling and the expression of VGLUT1 were decreased. A significant correlation was found between reduced expression of insulin receptor and VGLUT1. The administration of a JNK inhibitor reversed the decrease in VGLUT1 expression found in a mice model of insulin resistance. It is suggested that activation of JNK in AD inhibits insulin signaling which could lead to a decreased expression of VGLUT1, therefore contributing to the glutamatergic deficit in AD.
authors.affiliation: Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Perdigon
authors.affiliation: Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Solas
authors.affiliation: Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Maria Javier
authors.initials: MJ
authors.lastname: Ramirez
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*
chemical_list: D007328:Insulin; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C493464:SLC17A7 protein, human; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048670:MAP Kinase Kinase 4; D003345:Corticosterone
keywords: Glutamate; JNK; Mini-Mental State Examination; insulin; pAkt; postmortem human tissue