Chinese Journal of Integrative Medicine, Год журнала: 2023, Номер 30(8), С. 701 - 712
Опубликована: Ноя. 21, 2023
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Фев. 16, 2024
Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management
Язык: Английский
Процитировано
231
World Journal of Diabetes, Год журнала: 2024, Номер 15(7), С. 1430 - 1447
Опубликована: Июль 8, 2024
Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.
Язык: Английский
Процитировано
8
CNS Spectrums, Год журнала: 2025, Номер unknown, С. 1 - 6
Опубликована: Янв. 13, 2025
Abstract Incretin-based treatments, such as glucagon-like peptide-1 receptor (GLP-1R) agonists (eg liraglutide and semaglutide), have rapidly transformed obesity treatment. The well-documented weight loss effect from these agents is considered to be primarily a result of their actions on food intake, but frequent anecdotal reports varied sources suggested that they might also broadly affect consummatory behavior, including alcohol drugs abuse, suggesting potential modulatory reward behavior. Herein, we critically review the extant literature behavioral effects GLP-1R in humans, impact feeding alcohol/drug overall response. We consider physiological neurobiological underpinnings GLP-1 actions, with focus its distinct central peripheral roles, well relationships broader energy homeostasis network. conclude discussion implications this line research how behavior conceptualized, future directions for research.
Язык: Английский
Процитировано
1
Receptors, Год журнала: 2025, Номер 4(1), С. 2 - 2
Опубликована: Янв. 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
Язык: Английский
Процитировано
1
Nature Mental Health, Год журнала: 2025, Номер unknown
Опубликована: Фев. 13, 2025
Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel drugs approved for diabetes and obesity. They acknowledged as a major scientific breakthrough. In addition to their metabolic effects, these medications act on other bodily systems involved in the physiopathology of various neurological psychiatric disorders. Several stakeholders calling more research investigate repurposing potential GLP-1RAs cognitive mental disorders, while others advocate better assessment safety profile from neuropsychiatric perspective. this Analysis, we searched relevant literature effects across range illnesses, gathering describing available pre-clinical mechanistic (278 studies) clinical (96 evidence substance-use psychotic mood anxiety eating others. By leveraging translational insights data, consider implications practice propose avenues further research.
Язык: Английский
Процитировано
1
The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100111 - 100111
Опубликована: Фев. 1, 2025
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Emerging evidence suggests that antidiabetic agents may offer neuroprotective effects by targeting shared pathophysiological mechanisms such as insulin resistance and neuroinflammation. However, the comparative efficacy, safety of these in AD remain unclear. This study aimed to systematically evaluate compare efficacy for improving cognitive outcomes, reducing amyloid-β (Aβ) deposition, managing adverse patients AD, using network meta-analysis randomized controlled trials (RCTs). A comprehensive literature search was conducted across multiple databases identify RCTs examining AD. The primary outcomes included performance (e.g., MMSE scores), Aβ deposition (measured via CSF biomarkers), safety/adverse effects. performed integrate direct indirect evidence, ranking interventions Surface Under Cumulative Ranking (SUCRA) probabilities. Risk bias assessed Cochrane risk-of-bias tool. total 26 studies, involving 7,361 participants, were analysis. evaluated detemir (both low-dose high-dose), liraglutide, exenatide, metformin, pioglitazone. Both (mean difference: 2.10, 95 % CI: 1.04 3.15), high-dose 1.40, -0.07 2.88), exenatide 1.19, 0.06 2.32), metformin combined 1.06, -1.68 3.80) showed improvements compared placebo. Among these, demonstrated most significant improvement. In terms ranked highest effectiveness, SUCRA score (84.6), followed (SUCRA: 54.1). Low-dose 51.1) also moderate efficacy. some reduction -0.31, -2.82 2.20), although statistical significance limited. Liraglutide exhibited rate withdrawal 1.97, 4.00), while pioglitazone lowest rates 0.07, -0.03 0.17). provides valuable insights into improvement effect on deposition. Metformin emerged effective agent levels, though its function less pronounced. Safety profiles varied, liraglutide associated withdrawals, incidence treatment-related discontinuations. These findings support potential use agents, particularly detemir, therapeutic option further studies are needed confirm their long-term benefits safety.
Язык: Английский
Процитировано
1
Peptides, Год журнала: 2025, Номер 187, С. 171380 - 171380
Опубликована: Март 11, 2025
Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and dual tirzepatide that engages receptors for GLP-1 glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials 'real-world' confirmed marked glucose-lowering weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young elderly individuals without diabetes and/or overweight or obesity. also protections against development progression cardiovascular renal diseases are additive to benefits conferred by improved control blood glucose body weight. Emerging evidence suggests therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea possibly degenerative bone disorders cognitive decline. New incretin-based peptide in a long-acting glucagon (LY3324954), GLP-1/glucagon agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon (retatrutide, efocipegtrutide), combination amylin analogue cagrilintide (CagriSema), unimolecular GLP-1/amylin (amycretin), GIP antibody agonism (MariTide). The creation multi-targeting synthetic peptides provides opportunities management type 2 obesity as well new therapeutic approaches an expanding list associated co-morbidities. aim review is acquaint reader developments field from 2023 present (February 2025).
Язык: Английский
Процитировано
1
Journal of Endocrinological Investigation, Год журнала: 2024, Номер unknown
Опубликована: Сен. 20, 2024
Язык: Английский
Процитировано
6
Molecular Metabolism, Год журнала: 2024, Номер 89, С. 102019 - 102019
Опубликована: Авг. 30, 2024
The development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment type 2 diabetes and obesity has been accompanied by evidence anti-inflammatory cytoprotective actions in heart, blood vessels, kidney, brain. Whether GLP-1R might be useful clinically attenuating deterioration cognitive dysfunction reducing progression Alzheimer's disease remains uncertain. Here we evaluated semaglutide tirzepatide, distinct GLP-1 medicines, two mouse models neurodegeneration. Semaglutide reduced body weight improved glucose tolerance 12-month-old male female 5XFAD APP/PS1 mice, consistent with pharmacological engagement GLP-1R. Nevertheless, amyloid plaque density was not different cerebral cortex, hippocampus, or subiculum semaglutide-treated mice. IBA1 GFAP expression were increased hippocampus mice but semaglutide. Moreover, parameters neurobehavioral function using Open Field testing Morris water maze following To explore whether incretin therapies more effective younger studied tirzepatide action 6-month-old Neither nor modified extent accumulation, hippocampal IBA1+ GFAP+ cells, testing, despite improving weight. mRNA biomarkers inflammation neurodegeneration after tirzepatide. Collectively, these findings reveal preservation metabolic yet inability to detect improvement structural functional disease.
Язык: Английский
Процитировано
5
Frontiers in Neuroscience, Год журнала: 2024, Номер 18
Опубликована: Фев. 15, 2024
Although a wide variety of mechanisms take part in the secondary injury phase spinal cord (SCI), inflammation is most important factor implicated sequelae after SCI. Being central to reaction, macrophages and their polarization are topic that has garnered interest studies SCI injury. The glucagon-like peptide 1 (GLP-1) receptor agonist exenatide been shown enhance endoplasmic reticulum stress response improve motor function recovery (SCI). Since also reported induce production M2 cells models cerebral infarction neurodegenerative diseases, this study was conducted examine effects administration on process ensues In rat contusion model injury, group received subcutaneous injection 10 μg immediately while those control mL phosphate-buffered saline. Quantitative RT-PCR immunohistochemical staining were used evaluate infiltrating injured cord, especially with regard macrophage M1 profiles. changes hind limb assessed based Basso, Beattie, Bresnahan locomotor rating scale (BBB scale) scores. improvement BBB scores significantly higher from day 7 onwards. revealed an increase expression markers anti-inflammatory interleukins accompanied by decrease inflammatory cytokines. Immunohistochemical showed no significant difference numbers between two groups, but number observed 3 Our findings suggest promoted M2-phenotype SCI, which may have led
Язык: Английский
Процитировано
4