title: Glucagon-like peptide-1 protects the murine hippocampus against stressors via Akt and ERK1/2 signaling.
abstract: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death in the hippocampus and cerebral cortex. Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptides. GLP-1-associated medicines are widely used as treatments for type 2 diabetes. In addition, they have been shown to ameliorate pathology in AD mouse models. Here, we investigated the effects of GLP-1 on different stressors in murine hippocampal HT22 cells. GLP-1 (7-36) prevented H2O2-, l-glutamate-, tunicamycin-, thapsigargin-, and amyloid β1-42-induced neuronal cell death in a concentration-dependent manner. GLP-1 (7-36) treatment for 1 h significantly increased phosphorylated Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2) when compared with vehicle-treatment. These results suggest that GLP-1 (7-36) is protective against these stressors via activation of survival signaling molecules, such as Akt and ERK1/2 in HT22 cells. In conclusion, GLP-1 and activators of the GLP-1 receptor might be useful targets for the treatment of AD.
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Yuta
authors: Y
authors: Yoshino
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Mitsue
authors: M
authors: Ishisaka
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Saori
authors: S
authors: Tsujii
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D052216:Glucagon-Like Peptide 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Alzheimer's disease; Amyloid β(1)(–)(42); Endoplasmic reticulum stress; Glucagon-like peptide-1; HT22; Oxidative stress