JNK: A Putative Link Between Insulin Signaling and VGLUT1 in Alzheimer’s Disease

Article type: Short Communication

Authors: Rodriguez-Perdigon, Manuel^a | Solas, Maite^{a; b} | Ramirez, Maria Javier^{a; b; *}

Affiliations: [a] Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain | [b] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain

Correspondence: [*] Correspondence to: Dr. María J. Ramírez, Department of Pharmacology, School of Medicine, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain. Tel.: +34 948425600; Fax: +34 948425649; E-mail: mariaja@unav.es.

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.

Keywords: Glutamate, insulin, JNK, Mini-Mental State Examination, pAkt, postmortem human tissue

DOI: 10.3233/JAD-150659

Journal: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 963-967, 2016