Journal Article Review Epublish 11 citations
PubMed: 40430434 DOI: 10.3390/ph18050614
Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.
Pharmaceuticals (Basel) 18(5)
Authors: Melinda Urkon, Elek Ferencz, József Attila Szász, Monica Iudita Maria Szabo, Károly Orbán-Kis, Szabolcs Szatmári, Előd Ernő Nagy
Affiliations
- Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania.
- Service of Translational Medicine and Clinical Research, Emergency County Hospital Miercurea Ciuc, 530173 Miercurea Ciuc, Romania.
- Department M3, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania.
- 2nd Clinic of Neurology, Targu Mures County Emergency Clinical Hospital, 540136 Targu Mures, Romania.
- Clinic of Diabetology, Nutrition and Metabolic Disease, Targu Mures County Emergency Clinical Hospital, 540136 Targu Mures, Romania.
- Department of Physiology, M2, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania.
- Department of Biochemistry and Environmental Chemistry, F1, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania. Laboratory of Medical Analysis, Clinical County Hospital Mures, 540394 Targu Mures, Romania.
Abstract
In addition to the classically accepted pathophysiological features of Alzheimer's disease (AD), increasing attention is paid to the role of the insulin-resistant state of the central nervous system. Glucagon-like peptide-1 receptor (GLP-1R) agonism demonstrated neuroprotective consequences by mitigating neuroinflammation and oxidative damage. The present review aims to offer a comprehensive overview of the neuroprotective properties of GLP-1R agonists (GLP-1RAs), with a particular focus on experimental animal models of AD. Ameliorated amyloid-β plaque and neurofibrillary tangle formation and deposition following exenatide, liraglutide, and lixisenatide treatment was confirmed in several models. The GLP-1RAs studied alleviated central insulin resistance, as evidenced by the decreased serine phosphorylation of insulin receptor substrate 1 (IRS-1) and restored downstream phosphoinositide 3-kinase/RAC serine/threonine-protein kinase (PI3K/Akt) signaling. Furthermore, the GLP-1RAs influenced multiple mitogen-activated protein kinases (extracellular signal-regulated kinase: ERK; c-Jun N-terminal kinase: JNK, p38) positively and suppressed glycogen synthase kinase 3 (GSK-3β) hyperactivation. A lower proportion of reactive microglia and astrocytes was associated with better neuronal preservation following their administration. Finally, restoration of cognitive functions, particularly spatial memory, was also observed for semaglutide and dulaglutide. GLP-1RAs, therefore, hold promising disease-modifying potential in the management of AD.
MeSH
Glucagon-Like Peptide 1, Insulin Resistance, Glucagon-Like Peptide-1 Receptor, Insulin, Protein Kinases, Alzheimer Disease, Oxidative Stress, Extracellular Signal-Regulated Map Kinases, Jnk Mitogen-Activated Protein Kinases, Serine