» Articles » PMID: 28540646

The Molecular Mechanism of Glucagon-Like Peptide-1 Therapy in Alzheimer's Disease, Based on a Mechanistic Target of Rapamycin Pathway

Overview
Journal CNS Drugs
Specialties Neurology
Pharmacology
Date 2017 May 26
PMID 28540646
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

The mechanistic target of rapamycin (mTOR) is an important molecule that connects aging, lifespan, energy balance, glucose and lipid metabolism, and neurodegeneration. Rapamycin exerts effects in numerous biological activities via its target protein, playing a key role in energy balance, regulation of autophagy, extension of lifespan, immunosuppression, and protection against neurodegeneration. There are many similar pathophysiological processes and molecular pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), and pharmacologic agents used to treat T2DM, including glucagon-like peptide-1 (GLP-1) analogs, seem to be beneficial for AD. mTOR mediates the effects of GLP-1 analogs in the treatment of T2DM; hence, I hypothesize that mTOR is a key molecule for mediating the protective effects of GLP-1 for AD.

Citing Articles

A Systematic Review of Semaglutide's Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies.

Tipa R, Balan D, Georgescu M, Ignat L, Vacaroiu I, Georgescu D Int J Mol Sci. 2024; 25(9).

PMID: 38732190 PMC: 11084700. DOI: 10.3390/ijms25094972.


Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK.

Maiese K Cells. 2023; 12(22).

PMID: 37998330 PMC: 10670256. DOI: 10.3390/cells12222595.


Semaglutide Protects against 6-OHDA Toxicity by Enhancing Autophagy and Inhibiting Oxidative Stress.

Liu D, Zhao C, Wei X, Ma Y, Wu J Parkinsons Dis. 2022; 2022:6813017.

PMID: 35873704 PMC: 9300292. DOI: 10.1155/2022/6813017.


The interplay between oxidative stress and autophagy: focus on the development of neurological diseases.

Talebi M, Mohammadi Vadoud S, Haratian A, Talebi M, Farkhondeh T, Pourbagher-Shahri A Behav Brain Funct. 2022; 18(1):3.

PMID: 35093121 PMC: 8799983. DOI: 10.1186/s12993-022-00187-3.


Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.

Querfurth H, Lee H Mol Neurodegener. 2021; 16(1):44.

PMID: 34215308 PMC: 8252260. DOI: 10.1186/s13024-021-00428-5.


References
1.
de la Monte S, Re E, Longato L, Tong M . Dysfunctional pro-ceramide, ER stress, and insulin/IGF signaling networks with progression of Alzheimer's disease. J Alzheimers Dis. 2012; 30 Suppl 2:S217-29. PMC: 4562691. DOI: 10.3233/JAD-2012-111728. View

2.
Shingo A, Kanabayashi T, Kito S, Murase T . Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behav Brain Res. 2012; 241:105-11. DOI: 10.1016/j.bbr.2012.12.005. View

3.
Kimura R, Okouchi M, Fujioka H, Ichiyanagi A, Ryuge F, Mizuno T . Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. Neuroscience. 2009; 162(4):1212-9. DOI: 10.1016/j.neuroscience.2009.05.025. View

4.
Zhu Y, Wang J . Wogonin increases β-amyloid clearance and inhibits tau phosphorylation via inhibition of mammalian target of rapamycin: potential drug to treat Alzheimer's disease. Neurol Sci. 2015; 36(7):1181-8. DOI: 10.1007/s10072-015-2070-z. View

5.
Chen Y, Tian Z, Liang Z, Sun S, Dai C, Lee M . Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer's disease. PLoS One. 2012; 7(12):e51432. PMC: 3517562. DOI: 10.1371/journal.pone.0051432. View