Faculty Collaboration Database

[Neuroprotective effects of a novel antidiabetic drug (D-Ser2)Oxm on amyloid β protein-induced cytotoxicity]. Sheng Li Xue Bao 2016 Jun 25;68(3):265-75

Date

06/29/2016

Pubmed ID

27350199

Scopus ID

2-s2.0-85021389578 (requires institutional sign-in at Scopus site)   4 Citations

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.

Author List

Han YF, Holscher C, Wang ZJ, Zhang J, Yuan L, Tong JQ, Wang DD, Wu MN, Qi JS

Author

Jiaqing Tong PhD Postdoctoral Researcher 3 in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amyloid beta-Peptides
Animals
Calcium
Cell Survival
Diabetes Mellitus, Type 2
Glucagon-Like Peptide-1 Receptor
Hippocampus
Hypoglycemic Agents
Insulin
Membrane Potential, Mitochondrial
Neurogenesis
Neurons
Neuroprotective Agents
Rats