Ginecologia ro, Journal Year: 2024, Volume and Issue: 4(46), P. 42 - 42
Published: Jan. 1, 2024
Receptors, Journal Year: 2025, Volume and Issue: 4(1), P. 2 - 2
Published: Jan. 26, 2025
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including dulaglutide, liraglutide, semaglutide, and exenatide, are effective treatments for type 2 diabetes mellitus (T2DM) obesity. These agents mimic the action of endogenous incretin glucagon-like (GLP-1) by enhancing insulin secretion, inhibiting glucagon release, promoting weight loss through appetite suppression. GLP-1RAs have recently been suggested to neuroprotective effects, suggesting their potential as treatment neurodegenerative disorders, such Alzheimer’s disease (AD). AD T2DM share several common pathophysiological mechanisms, resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction. shared mechanisms suggest that therapeutic targeting metabolic dysfunction may also be beneficial conditions. Preclinical studies on in models, both vitro vivo, demonstrated promising reductions amyloid-beta accumulation, decreased tau hyperphosphorylation, improved synaptic plasticity, enhanced neuronal survival. Despite encouraging results from preclinical challenges need addressed before can widely used treatment. Ongoing clinical trials investigating cognitive benefits patients, aiming establish role a option AD. This review aimed examine current literature GLP-1
Language: Английский
Citations
1
Brain Sciences, Journal Year: 2024, Volume and Issue: 14(12), P. 1191 - 1191
Published: Nov. 26, 2024
Background/Objectives: Diabetes mellitus (DM), a widespread endocrine disorder characterized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer’s disease (AD). Effective blood glucose management is essential, sitagliptin (SITG), dipeptidyl peptidase-4 (DPP-4) inhibitor, may offer neuroprotective benefits in type 2 diabetes (T2DM). Methods: T2DM was induced rats using nicotinamide (NICO) streptozotocin (STZ), biomarkers AD DM-linked enzymes, inflammation, oxidative stress, apoptosis were evaluated brain. Computational studies supported vivo findings. Results: SITG significantly reduced brain enzyme levels acetylcholinesterase (AChE), beta-secretase-1 (BACE-1), DPP-4, glycogen synthase kinase-3β (GSK-3β) T2DM-induced rats. It also inflammation lowering cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB). Additionally, improved stress markers reducing malondialdehyde (MDA) enhancing glutathione (GSH). increased anti-apoptotic B-cell lymphoma protein-2 (Bcl-2) while pro-apoptotic Bcl-2-associated X (BAX) Caspace-3. lowered plasma insulin levels. To explore potential molecular level mechanisms, docking performed on AChE, COX-2, GSK-3β, BACE-1, The binding affinity for above-mentioned target enzymes 10.8, 8.0, 9.7, 7.7, 7.9 kcal/mol, respectively, comparable to co-crystallized ligands. Further mode analysis lowest energy conformation revealed interactions with critical residues. Conclusions: These findings highlight SITG’s targets T2DM-associated neurodegeneration its therapeutic approach AD, warranting further clinical investigations.
Language: Английский
Citations
3
Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 106413 - 106413
Published: Nov. 1, 2024
Language: Английский
Citations
2
The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Journal Year: 2024, Volume and Issue: 60(1)
Published: Nov. 11, 2024
Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, cognitive decline. Despite advances in understanding AD pathophysiology the expansion of therapeutic options over past three decades, remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring need for innovative treatment approaches beyond symptomatic relief. This calls re-examination pathology identify potential targets that go conventional strategies. review highlights four most promising non-canonical targets: oligodendrocytes, blood–brain barrier (BBB), neuroimmunometabolism, coagulation system. These components are crucial maintaining integrity proper function neurons brain, playing key roles progression AD. Oligodendrocytes, example, essential myelination neuronal support, while BBB dysfunction can lead impaired clearance toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses brain dysregulation system has been linked increased neuroinflammation vascular abnormalities Recent discoveries these fields provide new avenues identifying targets. By exploring pathways, future research may offer breakthroughs treating moving management towards disease-modifying
Language: Английский
Citations
1
Ginecologia ro, Journal Year: 2024, Volume and Issue: 4(46), P. 42 - 42
Published: Jan. 1, 2024
Citations
0