Caveolae with GLP-1 and NMDA Receptors as Crossfire Points for the Innovative Treatment of Cognitive Dysfunction Associated with Neurodegenerative Diseases DOI Creative Commons

Moeka Nakashima,

Naoko Suga,

Sayuri Yoshikawa

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(16), P. 3922 - 3922

Published: Aug. 20, 2024

Some neurodegenerative diseases may be characterized by continuing behavioral and cognitive dysfunction that encompasses memory loss and/or apathy. Alzheimer’s disease is the most typical type of such are deficits cognition alterations behavior. Despite huge efforts against disease, there has yet been no successful treatment for this disease. Interestingly, several possible risk genes frequently expressed within brain cells, which also linked to cholesterol metabolism, lipid transport, exosomes, caveolae formation, suggesting a therapeutic target dysfunctions. modulation autophagy/mitophagy with alteration glucagon-like peptide-1 (GLP-1) N-methyl-d-aspartate (NMDA) receptor signaling offer novel approach preventing alleviating dysfunction. A paradigm showing both GLP-1 NMDA receptors at sites promising crucial targets dysfunctions presented here, able modify progression This research direction create potential move clinical care toward disease-modifying strategies maximal benefits patients without detrimental adverse events diseases.

Language: Английский

Engineered MXene Biomaterials for Regenerative Medicine DOI

Shengmin Zhang,

Liang Wang, Zhichao Feng

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

MXene-based materials have attracted significant interest due to their distinct physical and chemical properties, which are relevant fields such as energy storage, environmental science, biomedicine. MXene has shown potential in the area of tissue regenerative medicine. However, research on its applications regeneration is still early stages, with a notable absence comprehensive reviews. This review begins detailed description intrinsic properties MXene, followed by discussion various nanostructures that can form, spanning from 0 3 dimensions. The focus then shifts biomaterials engineering, particularly immunomodulation, wound healing, bone regeneration, nerve regeneration. MXene's physicochemical including conductivity, photothermal characteristics, antibacterial facilitate interactions different cell types, influencing biological processes. These highlight modulating cellular functions essential for Although developing, versatile structural attributes suggest role advancing

Language: Английский

Citations

6
GLP-1 and the Neurobiology of Eating Control: Recent Advances DOI Creative Commons
Lauren A. Jones, Daniel I. Brierley

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

Published: Jan. 15, 2025

Abstract Obesity is now considered a chronic relapsing progressive disease, associated with increased all-cause mortality that scales bodyweight, affecting more than 1 billion people worldwide. Excess body fat strongly excess energy intake, and most successful anti-obesity medications (AOMs) counter this positive balance through the suppression of eating to drive weight loss. Historically, AOMs have been characterised by modest loss side effects which are compliance-limiting, in some cases life-threatening. However, field obesity pharmacotherapy has entered new era based on analogues gut hormone neuropeptide glucagon-like peptide-1 (GLP-1). The latest versions these drugs elicit unprecedented levels clinical trials, starting be substantiated real-world usage. Notably, reduce primarily reducing via activation GLP-1 receptor multiple sites action CNS, although relevant action, neural circuits recruited remain contentious. Here we provide targeted synthesis recent developments neurobiology, highlighting studies advanced our understanding how signalling modulates eating, identify open questions future challenges believe still need addressed aid prevention and/or treatment obesity.

Language: Английский

Citations

2
Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment DOI Creative Commons

Qibo Huang,

Bai Hu,

Zhang Ping

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

The study of the multifaceted interactions between neuroscience and cancer is an emerging field with significant implications for understanding tumor biology innovation in therapeutic approaches. Increasing evidence suggests that neurological functions are connected tumorigenesis. In particular, peripheral central nervous systems, synapse, neurotransmitters, neurotrophins affect progression metastasis through various regulatory approaches immune microenvironment. this review, we summarized tumorigenesis metastasis, which controlled by systems. We also explored roles neurotransmitters progression. Moreover, examined interplay system have identified drugs target treatment. review present work supporting agent targeting could potential to improve therapy.

Language: Английский

Citations

2
Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: a systematic review DOI Creative Commons

Wael Halloum,

Yousef Al Dughem,

Dagmar Beier

et al.

The Journal of Headache and Pain, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 12, 2024

Abstract Background Glucagon-like peptide-1 (GLP-1) plays a crucial role in metabolic disorders by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying, thereby improving glycemic control. In recent years, GLP-1 neuronal pathways has expanded its therapeutic potential. We aim to comprehensively evaluate the relevance of headache pain disorders. Methods A systematic literature search was conducted on PubMed Embase (Ovid) databases using terms “GLP-1” “pain”. Animal human studies published English language were included. Abstracts, reviews, articles other than “pain” excluded. Results The strategy identified 833 hits, which 42 included final review. categorized into four groups: inflammatory osteoarthritis, headaches, neuropathic diabetic neuropathy, visceral irritable bowel syndrome. receptor (GLP-1R) agonists, like liraglutide, have shown analgesic effects modulating hypersensitivity animal models pain. is involved migraine mechanisms GLP-1R agonists are beneficial individuals with idiopathic intracranial hypertension. Additionally, reduce ameliorate symptoms patients Conclusions scope expanding beyond traditional targets, highlighting potential for Engineering bimodal molecules that integrate agonism specific pain-related may offer innovative options.

Language: Английский

Citations

11
Constitutive loss of kynurenine-3-monooxygenase changes circulating kynurenine metabolites without affecting systemic energy metabolism DOI
Kyle Dumont, Paulo R. Jannig,

Margareta Porsmyr‐Palmertz

et al.

AJP Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: 328(2), P. E274 - E285

Published: Jan. 13, 2025

Kynurenic acid (KYNA) and quinolinic (QUIN) are metabolites of the kynurenine pathway tryptophan degradation with opposing biological activities in central nervous system. In periphery, KYNA is known to positively affect metabolic health, whereas effects QUIN remain less explored. Interestingly, stressors, including exercise obesity, differentially change balance between circulating QUIN. Here, we hypothesized that chronically elevated levels reduced would manifest as differences whole body energy metabolism. To test this, used a mouse model lacking enzyme 3-monooxygenase (KMO), thus shunting away from synthesis toward production. KMO-deficient wild-type littermate male female mice were evaluated under chow high-fat diets. Comprehensive metabolite profiling plasma showed loss KMO elicits robust changes metabolites. This included 45-fold increase kynurenine, 26-fold KYNA, 99% decrease levels, depending on diet. However, despite these changes, did not significantly impact metabolism or transcriptomic profile subcutaneous adipose tissue either With inhibitors being considered therapeutic candidates for various disorders, this work shows chronic systemic inhibition does have widespread effects. Our data also indicate beneficial may depend its acute, intermittent elevation circulation, akin transient exercise-induced signals mediate improved health.NEW & NOTEWORTHY The influenced by stressors: raises while obesity linked increased We investigated whether KMO-leading decreased QUIN-would exhibit found was largely unaffected metabolites, suggesting

Language: Английский

Citations

1
Effects of systemic oxytocin and beta‐3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet‐induced obese rats DOI Creative Commons

Jared D. Slattery,

June R. Rambousek,

Edison Tsui

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 4, 2025

Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that [fourth ventricle (4V)] administration could be used as an adjunct to drugs directly target beta-3 adrenergic (β3-AR) elicit weight loss diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can with β3-AR agonist, CL 316243, increase BAT thermogenesis DIO rats. hypothesized agonist (CL 316243) treatment would produce additive effect reduce body adiposity rats by decreasing stimulating To test this hypothesis, we determined effects (subcutaneous) infusions (50 nmol/day) or vehicle (VEH) when combined daily (intraperitoneal) injections 316243 (0.5 mg/kg) VEH on weight, adiposity, temperature (T IBAT ). monotherapy decreased 8.0 ± 0.9% ( P <0.05) 8.6 0.6% <0.05), respectively, but combination produced more substantial (14.9 1.0%; compared either alone. These were associated energy elevated T during period. The findings from current study suggest are appear driven primarily OT-elicited changes 316243-elicited increases

Language: Английский

Citations

1
The neurobiology of overeating DOI Creative Commons
Garret D. Stuber, Valérie Schwitzgebel, Christian Lüscher

et al.

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

Published: April 1, 2025

Food intake serves to maintain energy homeostasis; however, overeating can result in obesity, which is associated with serious health complications. In this review, we explore the intricate relationship between overeating, and underlying neurobiological mechanisms. We review homeostatic hedonic feeding systems, highlighting role of hypothalamus reward systems controlling food balance. Dysregulation both these leads as seen genetic syndromes environmental models affecting appetite regulation when consuming highly palatable food. The concept "food addiction" examined, drawing parallels drug addiction. discuss cellular substrate for addiction-related behavior current pharmacological obesity treatments-in particular, GLP-1 receptor agonists-showcasing synaptic plasticity context exposure. A comprehensive model integrating insights from addiction research proposed guide effective interventions maladaptive behaviors. Ultimately, unraveling basis holds promise addressing pressing public issue obesity.

Language: Английский

Citations

1
The agony and the efficacy: central mechanisms of GLP-1 induced adverse events and their mitigation by GIP DOI Creative Commons
Jonathan D. Douros, Jonathan N. Flak,

Patrick J. Knerr

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

The agony and the efficacy: central mechanisms of GLP-1 induced adverse events their mitigation by GIP

Language: Английский

Citations

0
Taurine promotes glucagon‐like peptide‐1 secretion in enteroendocrine L cells DOI Creative Commons

Yuri Osuga,

Kazuki Harada, Toshimasa Yamauchi

et al.

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Taurine, an amino‐sulfonic acid mainly sourced from food, suppresses blood glucose by stimulating insulin secretion pancreatic β‐cells. However, its relationship with glucagon‐like peptide‐1 (GLP‐1) enteroendocrine L cells is unclear. This study aimed to determine the role of taurine in GLP‐1 cells. Taurine administration promoted cell line GLUTag and increased plasma mice. uptake via transporter cytosolic ATP levels, resulting higher intracellular Ca 2+ concentrations enhanced through ATP‐sensitive K + channel closure. These findings may help identify new therapeutic targets for obesity diet‐related disease prevention.

Language: Английский

Citations

0
Artificial intelligence in anti-obesity drug discovery: unlocking next-generation therapeutics DOI Creative Commons

Amit Gangwal,

Antonio Lavecchia

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104333 - 104333

Published: March 1, 2025

Obesity, a multifactorial disease linked to severe health risks, requires innovative treatments beyond lifestyle changes and current medications. Existing anti-obesity drugs face limitations regarding efficacy, side effects, weight regain high costs. Artificial intelligence (AI) is emerging as pivotal tool in drug discovery, expediting the identification of novel candidates optimizing treatment strategies. This review examines AI's potential developing next-generation therapeutics, with focus on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) their role discovering peptides. Additionally, it explores integration challenges offers future perspectives leveraging AI reshape landscape discovery.

Language: Английский

Citations

0