A novel DPP-4 inhibitor Gramcyclin A attenuates cognitive deficits in APP/PS1/tau triple transgenic mice via enhancing brain GLP-1-dependent glucose uptake.
Phytother Res
; 36(3): 1297-1309, 2022 Mar.
Article
in En
| MEDLINE
| ID: mdl-35088915
ABSTRACT
Enhancing glucagon-like peptide 1 (GLP-1) signaling with a dipeptidyl peptidase IV (DPP-4) inhibitor might exert protective effects on Alzheimer's disease (AD). We found that intragastric administration of Gramcyclin A (10, 20 and 40 mg/kg), a novel DPP-4 inhibitor, for 3 months significantly reversed cognitive decline in APP/PS1/tau triple transgenic mice in a dose-dependent manner. Gramcyclin A treatment markedly reduced Aß plaques as well as the insoluble and soluble forms of Aß40 and Aß42 in the hippocampus of APP/PS1/tau mice. Treatment with Gramcyclin A remarkedly decreased the level of microglia and suppressed neuroinflammation in the hippocampus of APP/PS1/tau mice. Moreover, Gramcyclin A treatment could increase brain glucose uptake in APP/PS1/tau mice, as detected by 18-fluoro-2-deoxyglucose (18 F-FDG) micro-positron emission tomography (micro-PET) imaging. Furthermore, Gramcyclin A significantly increased expression of glucagon-like peptide-1 (GLP-1), GLP-1R, proliferator-activated receptor gamma coactivator (PGC)-1α and glucose transporter 4 (GLUT4), and inhibited insulin receptor (IRS)-1 phosphorylation and tau hyperphosphorylation in the hippocampus of APP/PS1/tau mice. Collectively, Gramcyclin A conferred protective effects against AD via enhancing brain GLP-1-dependent glucose uptake. The DPP-4 inhibitor Gramcyclin A might be a potential therapeutic drug for AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dipeptidyl-Peptidase IV Inhibitors
/
Alzheimer Disease
/
Cognitive Dysfunction
Limits:
Animals
Language:
En
Journal:
Phytother Res
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2022
Type:
Article
Affiliation country:
China