Pharmacological Research, Год журнала: 2024, Номер 209, С. 107473 - 107473
Опубликована: Окт. 18, 2024
Язык: Английский
Pharmacological Research, Год журнала: 2025, Номер 212, С. 107610 - 107610
Опубликована: Янв. 17, 2025
Язык: Английский
Процитировано
2
Diabetes & Metabolism, Год журнала: 2025, Номер unknown, С. 101623 - 101623
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
2
Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107702 - 107702
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107701 - 107701
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2025, Номер unknown, С. jnnp - 335593
Опубликована: Апрель 10, 2025
Disease-modifying treatments for major neurocognitive disorders, including Alzheimer’s disease, Parkinson’s disease and other cognitive deficits, are among the main unmet needs in modern medicine. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently licensed treatment of type 2 diabetes mellitus obesity, offer a novel, multilayered mechanism intervention neurodegeneration through intermediate, aetiology-agnostic pathways, likely involving metabolic, inflammatory several relevant neurobiological processes. In vitro animal studies have revealed promising signals neuroprotection, with preliminary supportive evidence emerging from recent pharmacoepidemiological investigations clinical trials. this article, we comprehensively review that investigate impact GLP-1RAs on various aetiologies impairment dementia syndromes. Focusing human studies, highlight how brain energy homeostasis, neurogenesis, synaptic functioning, neuroinflammation cellular stress responses, pathological protein aggregates, proteostasis, cerebrovascular system blood-brain barrier dynamics may underlie GLP-1RA putative neuroprotective effects. We then report appraise observational investigations, trials pooled analyses. Finally, discuss current challenges perspectives ahead research implementation care people their individual penetrance potential, need response biomarkers stage-based indications, possible non-specific effects health, profile terms adverse events unwanted effects, lack long-term data efficacy safety, issues surrounding cost availability treatment.
Язык: Английский
Процитировано
0
Computer Methods and Programs in Biomedicine, Год журнала: 2025, Номер unknown, С. 108799 - 108799
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Diabetes & Metabolism, Год журнала: 2025, Номер unknown, С. 101655 - 101655
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown
Опубликована: Май 7, 2025
Abstract Aim Type 2 diabetes mellitus (T2DM) is associated with an increased risk of delirium and mortality. While glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) provide metabolic neuroprotective benefits, their long‐term impact on remains uncertain. This study compares GLP‐1 RAs metformin in relation to mortality T2DM patients using real‐world data. Methods A retrospective cohort was conducted the TriNetX global federated research network, which primarily comprises U.S.‐based healthcare organisations (approximately 85%), additional sites Europe, Asia‐Pacific Middle East. Adults (≥18 years) who initiated or were included. Propensity score matching (PSM) balances baseline characteristics. The primary outcome incident delirium; secondary all‐cause Kaplan–Meier survival curves time‐dependent Cox models assessed associations. Results After 1:1 PSM ( N = 63 096 per group), showed no overall reduction (AHR: 0.98, 95% CI: 0.94–1.02, p 0.3628). However, they protective first 5 years 0.89, 0.86–0.92, < 0.0001) but between 10 1.15, 1.04–1.26, 0.0046). Subgroup analysis revealed lower middle‐aged (40–79 those HbA1c <7.5%. Higher observed Asian Native Hawaiian/Pacific Islander populations. these findings should be interpreted caution due relatively small subgroup sizes limited representativeness groups within predominantly database, together accounted for less than 5% cohort. Mortality absolute terms (6.28% vs. 9.95%) higher hazard 1.16, 1.12–1.21, 0.001). Conclusions RA use initially a delirium, this association reversed over time. variations suggest individualised treatment considerations. Metformin preferred option given its stable cognitive benefits.
Язык: Английский
Процитировано
0
Aging Cell, Год журнала: 2025, Номер unknown
Опубликована: Май 10, 2025
ABSTRACT Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Metabolic dysfunctions, particularly type 2 diabetes mellitus (T2DM), have been implicated in AD pathogenesis, highlighting the potential for novel therapeutic approaches targeting shared underlying mechanisms. Here, we investigate sodium‐glucose cotransporter (SGLT2) inhibition as strategy using Enavogliflozin, potent SGLT2 inhibitor, 5XFAD mouse model. Five‐month‐old mice were treated with Enavogliflozin (0.1 or 1 mg/kg) vehicle 8 weeks. The higher dose significantly improved performance Y‐maze and Morris Water Maze tests, which correlated enhanced synaptic plasticity increased acetylcholine levels. Moreover, treatment reduced Aβ pathology plaque burden, affecting larger plaques. Mechanistically, attenuated neuroinflammation suppressing NF‐κB signaling proinflammatory cytokine production while promoting microglial recruitment to In vitro ex vivo analyses further revealed that enhances phagocytic capacity via AMPK‐mediated mitochondrial biogenesis function. These findings highlight multifaceted neuroprotective effects of AD, demonstrating its mitigate improve By uncovering impact on function, this study establishes promising avenue other disorders.
Язык: Английский
Процитировано
0
Molecules, Год журнала: 2024, Номер 29(24), С. 5936 - 5936
Опубликована: Дек. 16, 2024
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, it pathologically characterized by the accumulation of amyloid plaques neurofibrillary tangles in brain. Although various hypotheses have been proposed to explain pathogenesis AD, including beta hypothesis, oxidative stress abnormal phosphorylation tau proteins, exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited. Epidemiologic studies provide convincing evidence for significant association between type 2 diabetes AD. Here, we showed energy metabolism using glucose, lactate, ketone bodies, lipids as substrates normal brain, changes such due diabetes. We also influences altered on pathology comprehensively searched risk factors related possible therapeutic interventions based considering brain development
Язык: Английский
Процитировано
1