sitagliptin-phosphate and Nerve-Degeneration

Glucagon-like peptide-1 (GLP-1) signaling in the brain plays an important role in the regulation of glucose metabolism, which is impaired in Alzheimer's disease (AD). Here, we detected the GLP-1 and GLP-1 receptor (GLP-1R) in AD human brain and APP/PS1/Tau transgenic (3xTg) mice brain, finding that they were both decreased in AD human and mice brain. Enhanced GLP-1 exerts its protective effects on AD, however, this is rapidly degraded into inactivated metabolites by dipeptidyl peptidase-4 (DPP-4), resulting in its extremely short half-time. DPP-4 inhibitors, thus, was applied to improve the level of GLP-1 and GLP-1R expression in the hippocampus and cortex of AD mice brains. It is also protected learning and memory and synaptic proteins, increased the O-Glycosylation and decreased abnormal phosphorylation of tau and neurofilaments (NFs), degraded intercellular β-amyloid (Aβ) accumulation and alleviated neurodegeneration related to GLP-1 signaling pathway.

Topics: Adamantane; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Cerebral Cortex; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycosylation; Hippocampus; Humans; Intermediate Filaments; Learning; Memory Disorders; Mice; Mice, Transgenic; Nerve Degeneration; Phosphorylation; Signal Transduction; Sitagliptin Phosphate; tau Proteins