Neuroprotective Effect of SGLT2 Inhibitors
| Autor: | Paulina Gorzelak-Pabiś, Agnieszka Pawlos, Ewelina Woźniak, Marlena Broncel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
type 2 diabetes mellitus
Central nervous system Pharmaceutical Science Organic chemistry Brain damage Review sodium-glucose cotransporter 2 inhibitors Pharmacology Neuroprotection Analytical Chemistry Proinflammatory cytokine QD241-441 Sodium-Glucose Transporter 2 Drug Discovery Empagliflozin medicine oxidative stress Animals Humans Hypoglycemic Agents Cognitive Dysfunction SGLT2i Physical and Theoretical Chemistry Sodium-Glucose Transporter 2 Inhibitors PI3K/AKT/mTOR pathway cognitive impairment Microglia business.industry atheroprotection Brain Inflammasome Atherosclerosis medicine.anatomical_structure Neuroprotective Agents Diabetes Mellitus Type 2 Chemistry (miscellaneous) inflammation mTOR Molecular Medicine neuroprotection medicine.symptom business medicine.drug |
| Zdroj: | Molecules, Vol 26, Iss 7213, p 7213 (2021) Molecules |
| ISSN: | 1420-3049 |
| Popis: | Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) are newer hypoglycemic agents with many pleiotropic effects. In this review, we discuss their neuroprotective potential. SGLT2 inhibitors (SGLT2i) are lipid-soluble and reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors are present in the central nervous system (CNS). Flozins are not fully SGLT2-selective and have an affinity for the SGLT1 receptor, which is associated with protection against ischemia/reperfusion brain damage. SGLT2i show an anti-inflammatory and anti-atherosclerotic effect, including reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition, as well as cIMT regression. They also mitigate oxidative stress. SGLT2i improve endothelial function, prevent remodeling and exert a protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes. Flozins are also able to inhibit AChE, which contributes to cognitive improvement. Empagliflozin significantly increases the level of cerebral BDNF, which modulates neurotransmission and ensures growth, survival, and plasticity of neurons. Moreover, they may be able to restore the circadian rhythm of mTOR activation, which is quite a novel finding in the field of research on metabolic diseases and cognitive impairment. SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus. |
| Databáze: | OpenAIRE |
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