title: [Neuroprotective effects of a novel antidiabetic drug (D-Ser2)Oxm on amyloid β protein-induced cytotoxicity].
abstract: The accumulation and neurotoxicity of amyloid β protein (Aβ) in the brain is one of major pathological hallmarks of Alzheimer's disease (AD). The effective drugs against Aβ have been still deficient up to now. According to a most recent study, (D-Ser2) Oxm, a new antidiabetic drug, not only improves the disorders in plasma glucose and insulin in type 2 diabetes mellitus (T2DM) rats, but also exerts positive effects on hippocampal neurogenesis and synaptogenesis. However, it is still unclear whether (D-Ser2)Oxm can directly protect cultured neurons against Aβ1-42-induced cytotoxicity. In the present study, we investigated the neuroprotective effects of (D-Ser2)Oxm on the cultured primary hippocampal neurons by testing the cell viability, neuronal apoptosis, mitochondrial membrane potential and intracellular calcium concentration. The results showed that treatment with (D-Ser2)Oxm effectively reversed Aβ1-42-induced decline in cell viability (P < 0.001), and this protective effect could be inhibited by the pretreatment with exendin(9-39), a GLP-1 receptor blocker. (D-Ser2)Oxm treatment also decreased Aβ1-42-induced neuronal early apoptosis and down-regulated apoptotic protein caspase3. Meantime, (D-Ser2)Oxm treatment inhibited Aβ1-42-induced [Ca(2+)]i elevation, mitochondrial membrane potential depolarization, and glycogen synthase kinase-3β (GSK3β) activation. These results suggest that (D-Ser2)Oxm can protect hippocampal neurons against Aβ1-42-induced cytotoxicity and this effect may be related to activation of GLP-1 receptors, regulation of intracellular calcium homeostasis and stabilization of mitochondrial membrane potential.
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Han
authors.affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Holscher
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Tong
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China. jinshunqi2009@163.com.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D002118:Calcium; D002470:Cell Survival; D003924:Diabetes Mellitus, Type 2; D000067757:Glucagon-Like Peptide-1 Receptor; D006624:Hippocampus; D007004:Hypoglycemic Agents; D007328:Insulin; D053078:Membrane Potential, Mitochondrial; D055495:Neurogenesis; D009474:Neurons; D018696:Neuroprotective Agents; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D018696:Neuroprotective Agents; D002118:Calcium