Glucagon-like peptide-1 receptor: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 18, 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and found primarily on surfaces various cell types within human body. This specifically interacts with GLP-1, key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, several other crucial biological functions. In recent years, GLP-1 medications have become focal point medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, broad development prospects. article thoroughly traces developmental milestones drugs, from initial discovery clinical application, detailing evolution diverse along distinct pharmacological properties. Additionally, this paper explores potential applications agonists (GLP-1RAs) fields such neuroprotection, anti-infection measures, reduction inflammation, enhancement cardiovascular function. It provides in-depth assessment effectiveness GLP-1RAs across multiple body systems-including nervous, cardiovascular, musculoskeletal, digestive systems. includes integrating latest trial data delving into signaling pathways mechanisms. primary goal emphasize extensive benefits using treating spectrum diseases, obesity, non-alcoholic fatty liver disease (NAFLD), neurodegenerative musculoskeletal forms cancer. ongoing new indications for drugs offers promising prospects further expanding interventions, showcasing field.

Language: Английский

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The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)

Expert Opinion on Drug Safety, Journal Year: 2023, Volume and Issue: 23(1), P. 47 - 55

Published: Dec. 13, 2023

Recently, the European Medicines Agency (EMA) received reports of suicidal thoughts and self-injury associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide semaglutide.

Language: Английский

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Mapping the effectiveness and risks of GLP-1 receptor agonists

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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Potential Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Cognitive Decline and Dementia in Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11301 - 11301

Published: July 11, 2023

Dementia is a permanent illness characterized by mental instability, memory loss, and cognitive decline. Many studies have demonstrated an association between diabetes dysfunction that proceeds in three steps, namely, diabetes-associated decrements, mild impairment (MCI; both non-amnesic MCI amnesic MCI), dementia [both vascular Alzheimer’s disease (AD)]. Based on this association, has been designated as type 3 mellitus. The underlying mechanisms comprise insulin resistance, inflammation, lipid abnormalities, oxidative stress, mitochondrial dysfunction, glycated end-products autophagy. Moreover, insulin-like growth factor-1 (IGF-1) to be involved. Insulin the brain neuroprotective role alters skills alteration of signaling determines beta-amyloid (Aβ) accumulation, turn promoting resistance. In complex mechanism, other triggers include hyperglycemia-induced overproduction reactive oxygen species (ROS) inflammatory cytokines, which result neuroinflammation, suggesting antidiabetic drugs may potential treatments protect against AD. Among these, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are most attractive due their actions synaptic plasticity, cognition cell survival. present review summarizes significant data concerning pathophysiological pharmacological dementia.

Language: Английский

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Targeting redox imbalance in neurodegeneration: characterizing the role of GLP-1 receptor agonists

Theranostics, Journal Year: 2023, Volume and Issue: 13(14), P. 4872 - 4884

Published: Jan. 1, 2023

Reactive oxygen species (ROS) have emerged as essential signaling molecules regulating cell survival, death, inflammation, differentiation, growth, and immune response.Environmental factors, genetic or many pathological condition such diabetes increase the level of ROS generation by elevating production advanced glycation end products, reducing free radical scavengers, increasing mitochondrial oxidative stress, interfering with DAG-PKC-NADPH oxidase xanthine pathways.Oxidative therefore accumulation intracellular ROS, determines deregulation several proteins caspases, damages DNA RNA, interferes normal neuronal function.Furthermore, play an role in polymerization, phosphorylation, aggregation tau amyloid-beta, key mediators cognitive function decline.At level, interfere methylation pattern various apoptotic factors related to promoting neurodegeneration.Only few drugs are able quench neurons.The cross-linking pathways between dementia suggest that antidiabetic medications can potentially treat dementia.Among drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs) been found reduce ameliorate function, protein aggregation, neuroinflammation, synaptic plasticity, learning, memory.The incretin hormone (GLP-1) is produced enteroendocrine L cells distal intestine after food ingestion.Upon interacting its (GLP-1R), it regulates blood glucose levels inducing insulin secretion, inhibiting glucagon production, slowing gastric emptying.No study has evidenced a specific GLP-1RA pathway quenches production.Here we summarize effects GLP-1RAs against overproduction discuss putative efficacy Exendin-4, Lixisenatide, Liraglutide treating decreasing ROS.

Language: Английский

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Role of metabolic dysfunction and inflammation along the liver–brain axis in animal models with obesity-induced neurodegeneration

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1069 - 1076

Published: May 17, 2024

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. Obesity-related conditions like type 2 diabetes non-alcoholic fatty liver exacerbate this relationship. Peripheral lipid accumulation, particularly in liver, initiates a cascade inflammatory processes that extend brain, influencing critical regulatory regions. Ceramide palmitate, key components, along with transporters lipocalin-2 apolipoprotein E, contribute neuroinflammation by disrupting blood–brain barrier integrity promoting gliosis. insulin resistance further exacerbates brain neuroinflammation. Preclinical interventions targeting peripheral metabolism signaling pathways have shown promise reducing animal models. However, translating these findings clinical practice requires investigation into human subjects. In conclusion, dysfunction, inflammation, are integral neurodegeneration. Understanding complex mechanisms holds potential for identifying novel therapeutic targets improving outcomes diseases.

Language: Английский

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Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer’s Disease: A Systematic Review

Journal of Alzheimer s Disease Reports, Journal Year: 2024, Volume and Issue: 8(1), P. 777 - 789

Published: March 15, 2024

Background: Alzheimer’s disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical are limited. Objective: A systematic review was performed to evaluate GLP-1 RAs for their potential target pathology and improve cognition. Methods: Searches were conducted via three different databases (PubMed, Embase, Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: ‘glucagon-like agonist’ ‘Alzheimer’s disease’, as well entry ‘GLP-1 RA’, ‘AD’, types RA: ‘liraglutide’, ‘exenatide’, ‘lixisenatide’. Results: total 1,444 screened. Six articles that met criteria (four randomized control trials [RCTs] two protocol studies). Two RCTs with amyloid-β tau biomarker endpoints did not observe an end treatment difference between placebo treated groups. In cognitive endpoints, there no RA showed metabolic benefits, such lower body mass index improved glucose levels on oral tolerance tests may mitigate decline cerebral metabolism show enhanced blood-brain transport capacity using 18 F-FDG PET, however, more data needed. Conclusions: therapy alter biomarkers nor improvements cognition but neuroprotective benefits.

Language: Английский

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Exploring the Role of GLP-1 Receptor Agonists in Alzheimer’s Disease: A Review of Preclinical and Clinical Evidence

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

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Risk of Glaucoma in Non-Diabetic Patients using a Glucagon Like Peptide-1 Receptor Agonist

Ophthalmology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Metformin’s Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1783 - 1783

Published: Feb. 19, 2025

This study examines the effects of metformin on brain functions focusing variability results reported in literature. While some studies suggest that may have neuroprotective diabetic patients, others report an insignificant impact cognitive function, or even a negative effect. We propose this inconsistency be due to intrinsic cellular-level among individuals, which we term "biovariance". Biovariance persists demographically homogeneous samples complex and stochastic biological processes. Additionally, metabolic actions metformin, including its influence neuroenergetics neuronal survival, produce different depending individual characteristics.

Language: Английский

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