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Multidisciplinary care of pediatric obesity and its impact on sleep: a review.

Front Sleep

Ravali Inja, Christopher Cielo

Pediatric obesity has emerged as a significant global health issue with multifaceted consequences, including its impact on sleep health. Obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) are among the serious sleep-related comorbidities in obese children, contributing to impaired quality of life, cognitive deficits, and cardiovascular risks. These conditions frequently coexist with other obesity-related complications such as insulin resistance, type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD). This review explores the importance of multidisciplinary care in addressing pediatric obesity, emphasizing early diagnosis, nutritional counseling, physical activity interventions, psychological support, and pharmacologic therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists. The role of global trends, academic performance, and wellbeing clinics are also discussed. Although promising, the use of GLP-1s and surgical interventions in pediatrics remains constrained by limited data, particularly concerning their impact on sleep disorders. Further research is essential to clarify the long-term effects of GLP-1 receptor agonists and bariatric surgery not only on obesity and sleep-related comorbidities such as OSA and OHS, but also on cognitive function, psychosocial wellbeing, and overall health outcomes-thereby informing evidence-based, multidisciplinary approaches to pediatric obesity management.

Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation.

Diabetes Metab J

Xin Li, Aikebaier Aili, Yusujiang Tusuntuoheti +3 more

Obesity serves as a predominant factor in the progression of metabolic syndrome and type 2 diabetes mellitus. While sleeve gastrectomy (SG) is a well-established surgical intervention, its impact on appetite-regulating hormones, such as ghrelin (GHRL), is limited. Sleeve gastrectomy combined with fundoplication (SGFD) has emerged as a potential strategy to improve metabolic outcomes by modifying both gastric anatomy and gut-brain signaling.

From darkness to light: Case report on afamelanotide-treatment in a 9-year-old child with erythropoietic protoporphyria.

JAAD Case Rep

Anna-Elisabeth Minder, Jasmin Barman-Aksözen

Long-acting GIPR agonist LY3537021 reduces body weight and fasting blood glucose in patients with T2D: Preclinical development and phase 1 randomized ascending dose studies.

Mol Metab

William Roell, Jorge Alsina-Fernandez, Hongchang Qu +13 more

Tirzepatide, a single-molecule dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor (R) agonist, has shown superiority in the reduction of blood glucose and body weight, above selective GLP-1R agonists, but the contribution of GIP to these effects remains incompletely understood.

Effects of DSS-induced intestinal disruption on egg quality and brain, liver, and ovarian follicle functions in laying hens.

Poult Sci

Muhammad Anang Aprianto, Jirapat Jaisue, Naoki Isobe +1 more

Intestinal disruptions, including morphological changes, barrier dysfunction, and inflammation, are associated with reduced egg production in laying hens. A previous study reported that oral administration of low-dose dextran sodium sulfate (DSS; 0.255 g/kg body weight) for 28 days caused slight intestinal disruption, resulting in decreased egg production and yolk size in the first week. These findings suggest that short-term DSS exposure may induce long-lasting effects on follicular development; however, the mechanisms underlying this early response remain unclear. This study aimed to investigate the mechanisms underlying the reduction in egg and yolk production during the first week. White Leghorn laying hens (350 days old) were divided into five groups: DSS-treated groups for 1 (DSS1), 2 (DSS2), and 7 (DSS7) consecutive days, and control groups receiving distilled water for 0 (CON0) and 7 (CON7) consecutive days. Egg parameters and serum corticosterone levels were assessed in the CON7 and DSS7 groups. At each time point, the birds were euthanized, and samples from the intestine, liver, granulosa cells (F1 and F5 follicles), hypothalamus, and pituitary gland were collected. Low-doses of DSS administration yielded the following results: (1) decreased claudin-1 (CLA-1) and claudin-5 (CLA-5) in the cecum in DSS1 and DSS2, while increased pro-inflammatory cytokines in the ileum and cecum in DSS2 and DSS7. (2) Increased sterol regulatory element binding protein-1 (SREBP-1), very low density lipoprotein-II (VLDL-II), and estrogen receptor alpha (Erα) in the liver in DSS7. (3) Decreased low-density lipoprotein receptor (LDLr) and lipoprotein receptor 8 (LR8) in the granulosa cells in DSS2, with increased CLA-1 and CLA-5 in DSS1; both patterns were reversed in DSS7. (4) Increased stress-related hormone synthesis in DSS1 and DSS7, and gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) gene expression in DSS1 and DSS2. These results suggest that slight intestinal disruption triggers a systemic stress response that impairs yolk precursor uptake and follicular function, leading to reduced egg weight and yolk size without affecting gonadotropin or yolk precursor production. After one week, a compensatory feedback response restored yolk precursor uptake and gonadotropin synthesis, but yolk size continued to decline. In conclusion, these findings suggest that short-term intestinal disruption serves as a key trigger for prolonged impairment of reproductive function and egg quality in laying hens.

Duck-egg white hydrolysate supplementation enhances muscle endurance and fatigue resistance during high-intensity exercise.

Poult Sci

Kai-Li Shang, Yi-Ling Lin, Christoper Caesar Yudho Sutopo +2 more

Recent processing advances, including separating and marinating duck yolks, provide alternatives to traditional salted duck eggs. However, separated duck-egg white remains a nutritious agricultural byproduct due to its unpleasant odor and low consumer acceptance. Duck-egg white hydrolysates (DEWHs), produced by protease-A hydrolysis, are rich in branched-chain amino acids (BCAAs) and imidazole dipeptides like carnosine and anserine. In mice undergoing high-intensity exercise, DEWH supplementation increased hindlimb muscle mass, soleus-muscle-fiber size, and performance in swimming and treadmill tests. DEWHs improved lactate clearance, stabilized post-exercise blood glucose, and elevated muscle and liver glycogen (p < 0.05). DEWHs also improved exercise-induced muscle injury markers (AST, BUN, and CK) and inflammatory cytokines (IL-1β, IL-6, and TNF-α), and decreased antioxidant capacities (reduced GSH, SOD, and GSH-Px) (p < 0.05). In C2C12 myotubes, DEWHs counteracted dexamethasone (Dex)-induced mitochondrial dysfunction, suppressed protein synthesis, and ATP depletion while decreased protein synthesis signaling (p-p70S6K/p70S6K and p-4EBP1/4EBP1), and upregulated protein degradation markers (p-FoxO1/FoxO1 and TRIM63) and mitochondrial biogenesis factors (NRF1 and PGC-1α) were also mitigated (p < 0.05). Additionally, DEWHs enhanced citrate synthase and cytochrome c oxidase activities, boosting ATP production (p < 0.05). These findings suggest DEWHs enhance muscular endurance, reduce fatigue, and mitigate oxidative and inflammatory responses by modulating protein turnover and energy production, offering a novel protein supplement and value-added use for duck-egg white byproduct surplus.

Effect of glucagon-like peptide-1 receptor agonists on histologic MASH: A meta-analysis of randomized controlled trials.

Hepatol Commun

Noppachai Siranart, Christopher C Thompson, Pichamol Jirapinyo

Metabolic dysfunction-associated steatohepatitis (MASH) is the most common chronic liver disease worldwide, with a particularly high incidence among individuals with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective weight loss agents, with growing evidence suggesting potential benefits in MASH. This study aimed to evaluate the efficacy and safety of GLP-1RAs in improving the histologic features of MASH.

The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities.

Clin Pharmacol Drug Dev

Nila Ganamurali, Sarvesh Sabarathinam

Obesity has emerged as a global health crisis requiring innovative therapeutic strategies beyond conventional approaches. While glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists have redefined pharmacological management, their limitations necessitate further innovation. Retatrutide (LY3437943), a novel triple agonist targeting GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors, represents a transformative advance in obesity pharmacotherapy. Phase 2 trials report unprecedented weight reductions, comparable to bariatric surgery, with additional benefits for metabolic comorbidities such as NASH and cardiovascular disease. Retatrutide exemplifies rational multi-agonist peptide engineering and signals a paradigm shift in systems pharmacology. This perspective underscores the urgent need for scientific engagement, equity considerations, and policy preparedness, positioning retatrutide as a watershed in obesity treatment and a blueprint for future poly-agonist therapies.

Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.

Hepatol Commun

Themis Thoudam, Ge Zeng, Hui Gao +5 more

Mitochondria-derived peptides (MDPs) are bioactive molecules encoded by small open reading frames within mitochondrial DNA (mtDNA). Humanin, the first MDP to be discovered, functions as a cytoprotective factor, protecting cells from stress-induced apoptosis. Subsequent discoveries expanded this family to include Mitochondrial Open-reading-frame of the Twelve S rRNA-c (MOTS-c), a key regulator of metabolic homeostasis and stress adaptation, and the Small Humanin-Like Peptides (SHLP1-6), which modulate mitochondrial bioenergetics and insulin sensitivity. MDPs play critical roles in liver homeostasis by maintaining mitochondrial function and metabolic balance. Intracellularly, they modulate mitochondrial activity, oxidative stress, and apoptosis, promoting hepatocyte survival. Extracellularly, they act in autocrine, paracrine, or endocrine manners, engaging receptors or signaling pathways to regulate nuclear gene expression and metabolic adaptation. Emerging evidence highlights their relevance in metabolic dysfunction-associated steatotic liver disease (MASLD). Humanin exerts hepatoprotective effects by inhibiting apoptosis and modulating lipid metabolism. MOTS-c activates AMPK, regulates nuclear gene expression, suppresses fibrotic and inflammatory signaling, and restores mitochondrial function in MASLD and fibrosis models. SHLPs, particularly SHLP2, enhance mitochondrial function and insulin sensitivity, supporting glucose homeostasis and mitigating oxidative stress. Collectively, MDPs establish a novel paradigm in mitochondrial signaling, extending mtDNA function beyond energy production. This review summarizes current insights into MDP biology and highlights its emerging therapeutic potential in chronic liver disease.

Efficacy and Safety of Retatrutide in the Treatment of Diabetes and/or Obesity Comorbid with Chronic Kidney disease: a Systematic Review and Meta-Analysis.

Maedica (Bucur)

Kumari Pallavi, Anshuman Chandra, Keshav Kumar +4 more

There are still substantial clinical challenges in treating patients who come with type 2 diabetes and/or obesity in addition to chronic kidney disease (CKD). Retatrutide, an innovative agent, represents a potential advancement in therapy; however, its performance and safety profile specifically in a CKD population are not fully determined yet. This meta-analysis and systematic review sought to consolidate existing research on the use of retatrutide in this comorbid patient group. A comprehensive literature search identified relevant randomized controlled trials for inclusion. Reductions in glycated hemoglobin (HbA1c) and body weight were the primary goals for evaluating effectiveness, whereas adverse events were used to evaluate safety. Eight studies were included in the present research work. A significant mean reduction in HbA1c of -1.04% (95% CI -1.42 to -0.67) and a noticeable loss in weight, reaching up to -24.2%, were both linked with retatrutide treatment. A subgroup analysis indicated that the glycemic benefits were dose-dependent, with lower doses (≤8 mg) demonstrating a greater HbA1c reduction (-1.39%) than higher doses (≥12 mg, -0.65%). Furthermore, secondary analyses pointed toward possible renoprotective effects, evidenced by a reduction in albuminuria. The safety profile is primarily characterized by gastrointestinal adverse events, which is anticipated for this drug class. In conclusion, retatrutide exhibits strong efficacy for improving glucose levels and promoting weight loss in patients with diabetes, obesity and CKD, displaying a distinctive dose-response pattern where lower doses may be more effective for glycemic control. Its potential for kidney protection is promising, though clinicians should be mindful of managing gastrointestinal tolerability.

Female Sexual Desire, Arousal, and Orgasmic Dysfunctions: A Systematic Review and Meta-Analysis of Treatment Options.

J Minim Invasive Gynecol

Rafaela Germano Toledo, William D Winkelman, Daniela Reyes-Gonzalez +4 more

To conduct a systematic review and meta-analysis of treatments for female sexual desire, arousal, and orgasmic dysfunction in patients without sexual pain conditions.

Transcriptomic analysis reveals pathway-specific targets for hyperlocomotion and social withdrawal in mouse models of schizophrenia.

Neuroscience

Xu Liu, Lin Yuan, Qian Chu +4 more

Schizophreniais a severe mental disorder with complex behavioral pathology and complexgenetic risk.Here, we performed an integrated transcriptomic analysis of the prefrontal cortexin two distinct male C57BL/6J mouse modelsof schizophrenia,the neurodevelopmental methylazoxymethanol acetate (MAM) model (n = 7) and the acute non-competitive N-methyl-D-aspartatereceptor (NMDAR) antagonist MK-801model (n = 6, control n  = 8),compared to that of human patients. Differentially expressed genes in the MK-801 model displayed a modest correlation with that of schizophrenia patients (r = 0.40, p = 2.7 × 10-6), higher than the MAM model (r = 0.15, p = 0.23), underscoring NMDAR antagonism's relevance to the core pathology of the disorder. Using weighted gene co-expression network analysis, we identified 28co-expression modules across the mouse models, with 11modules significantly associated with individual schizophrenia-related behavioral endophenotypes.Notably, the brown module (linked to hyperlocomotion, r = 0.55, p = 0.01) and the darkgrey module (associated with social withdrawal, r = -0.71, p = 3 × 10-4)were enriched in Wnt and PI3K/Akt signaling pathways, respectively.Pharmacological inhibition of these two pathways specifically rectified corresponding behavioral anomalies in the MK-801 model, highlighting the critical role of altered Wnt and PI3K/Akt signaling in these behavioral domains of schizophrenia-related behaviors and proposing new avenues for therapeutic intervention.

Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers.

Sci Adv

Juan Cheng, Peng Wu, Chenwen Li +5 more

Oral delivery of peptide therapeutics remains challenging due to gastrointestinal (GI) degradation and poor intestinal absorption. Here, we propose a self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery, integrating a hydrophilic polyethylene glycol segment, a reactive oxygen species (ROS)-responsive hydrophobic self-immolative module, and a hydrolyzable scaffold, which collectively enable spontaneous assembly into micelle-like nanoparticles. Using three anti-inflammatory peptides (KPV, Ac-QAW, and IRW), we demonstrated that the engineered conjugates exhibit remarkable GI stability, efficient mucus penetration, and ROS-responsive release at inflamed sites. In colitis mice, the KPV-based conjugate (proKPV) achieved a 3.8-fold greater colonic accumulation than free KPV, with enhanced efficacy even at a 20-fold lower dose. Beyond therapeutic effects in the colitis model, oral proKPV substantially accumulated in inflamed lungs and exhibited potent anti-inflammatory efficacy in mice with acute lung injury. Ac-QAW and IRW-based conjugates exhibited comparable benefits, underscoring SIPPC as a transformative paradigm for oral peptide therapeutics, offering substantial promise for clinical translation in inflammatory disorders.

A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice.

Diabetes Obes Metab

Iona Davies, Alexandra Turland, Hanh Duyen Tran +9 more

Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans.

Functional roles of NR4A transcription factors in GnRH regulation of gonadotropin gene expression and secretion in rat primary pituitary cells.

J Reprod Dev

Ryota Terashima, Yuta Tomiyama, Shiro Kurusu +1 more

Gonadotropin-releasing hormone (GnRH) tightly regulates the synthesis and the release of gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while the intracellular molecular mechanisms following GnRH signal for the regulation of transcription remains incompletely understood. In this study, we used primary culture of rat anterior pituitary cells to investigate the role of NR4A transcription factors (NR4A1, NR4A2, and NR4A3) in GnRH regulation of gonadotropin secretion. GnRH agonist stimulation rapidly and transiently increased Nr4a1, Nr4a2, and Nr4a3 expression within one hour, accompanied by a time-dependent increase in Fshb mRNA levels and the secretion of both FSH and LH. The knockdown of each Nr4a gene using siRNA significantly reduced Fshb expression under GnRH stimulation. Nr4a1 knockdown caused the most pronounced decrease in FSH secretion. Although Lhb and Cga mRNA levels were largely unaffected, LH secretion was consistently reduced following NR4A knockdown. These findings suggest that NR4A transcription factors act downstream of GnRH signaling to promote Fshb transcription and facilitate gonadotropin secretion, thereby modulating GnRH-dependent control of FSH and LH secretion.

[Hormones and skin pigmentation: fundamentals and clinical relevance].

Dermatologie (Heidelb)

Markus Böhm

Skin pigmentation by the endogenous pigment melanin is a highly coordinated process in which hormones play a crucial role. They are synthesized not only in classical endocrine organs but also in the skin itself, which acts as an independent endocrine organ. Among the endocrine target structures of the skin, the melanocortin 1 receptor (MC1R) is of particular importance. Via its high expression and tonic activity in melanocytes, as well as by binding to natural melanocortins such as α‑melanocyte-stimulating hormone (α-MSH), being generated in the skin following ultraviolet (UV) light irradiation, MC1R crucially contributes to the different skin phototypes. Gene mutations of MC1R resulting in defective cyclic adenosine monophosphate (cAMP)-mediated signalling can lead to a shift of the eumelanin/pheomelanin ratio towards the pro-oxidant, yellowish-orange pheomelanin. In patients with Addison's disease and associated syndromes, ectopic proopiomelanocortin syndrome and primary adrenal cortex insufficiency elevated melanocortin levels result in increased melanin content of the skin. Two synthetic melanocortins, afamelanotide (NDP-α-MSH) and setmelanotide, are currently approved in Germany. By targeting MC1R directly (afamelanotide) or as a bystander effect (setmelanotide), both agents increase the skin melanin content. Non-licenced synthetic melanocortins, on the other hand, are used as lifestyle products in an unregulated manner. Additional hormones regulating melanogenesis and skin pigmentation include estrogens, thyroid hormones, insulin, insulin-like growth-factor‑1 and melatonin. They are of physiological and clinical relevance during pregnancy and in patients with melasma and vitiligo. Autoimmune thyroid disorders and diabetes are associated with non-segmental vitiligo. Melatonin appears to have a lightening effect on skin pigmentation by melanin.

Social stress worsens colitis through β-adrenergic-driven oxidative stress in intestinal mucosal compartments.

Brain Behav Immun

Maria Elisa Caetano-Silva, Miranda E Hilt, Ivan Valishev +10 more

Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre-treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitors and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2), Dual oxidase maturation factor 2 (Duoxa2), and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8-fold, p < 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced α -diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious (C. rodentium) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2, Nos2, and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic expression of key oxidative enzymes, especially DUOX2, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase-driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD.

Acute Stress Attenuates Hepatic Ischemia-Reperfusion Injury via Hypothalamic CRH Neuron-Induced HPA Axis Activation.

CNS Neurosci Ther

Xiaoqi Lin, Dan Yang, Shuyang Wang +10 more

Hepatic ischemia-reperfusion injury (HIRI) is a pathologic process commonly encountered during liver surgery, which seriously threatens patient prognosis. Currently, effective interventions or preventive measures are still lacking. Notably, patients with liver disease commonly experience brief acute stress prior to surgery; however, the impact of acute stress on HIRI remains unclear.

The gatekeepers of growth: The neural roles and regulation of growth hormone-releasing hormone neurons.

J Neuroendocrinol

Bradley B Jamieson

The neuroendocrine control of growth is mediated by the hypothalamic-pituitary-somatic (HPS) axis. This involves the hypothalamic release of growth hormone-releasing hormone (GHRH), which stimulates the pituitary secretion of growth hormone (GH). GH subsequently promotes growth both directly and indirectly by stimulating insulin-like growth factor 1 (IGF1) release from the liver. While extensive research has focused on the actions and mechanisms of GH and IGF1, comparatively little attention has been given to how GHRH neurons themselves are regulated. This review aims to provide insight into how GHRH neurons are controlled, emphasizing their intrinsic electrophysiological properties and the broader brain circuitry involved in detecting physiological signals such as hormonal and metabolic status. Central to this regulation is the balance of excitatory and inhibitory inputs that generate the pulsatile secretion pattern essential for growth regulation. Somatostatin (SST) provides critical inhibitory control over both GH secretion and GHRH neuronal activity. Feedback from peripheral hormones and integration of environmental and metabolic cues can further shape GHRH neuron function. Developmental, sex-dependent, and species-specific variations in GHRH neuron regulation are also discussed, highlighting important avenues for future research. This review offers a neuroendocrine perspective on growth regulation, with important implications for understanding the brain's role in regulating growth and development.

Preclinical evidence and therapeutic perspectives on carnosine for the treatment of neurodegenerative disorders.

AIMS Neurosci

Saviana Antonella Barbati, Giuseppe Carota, Konstantinos Partsinevelos +14 more

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely distributed in mammalian tissues, especially skeletal and cardiac muscle cells, and, to a lesser extent, in the brain. While early interest in carnosine was given because of its role in muscle cell metabolism and athletic performance, it has more recently gained attention for its potential application in several chronic diseases. Specifically, brain aging and neurodegenerative disorders have received particular attention, as a marked reduction in carnosine levels has been described in these conditions. Carnosine exerts a wide range of biological activities, including antioxidant, anti-inflammatory, anti-glycation, metal-chelating, and neuroprotective properties. Mechanistically, it acts by inhibiting the production of advanced glycation end products (AGEs), buffering cellular pH, and regulating intracellular nitric oxide signaling and mitochondrial function. Its safety profile, the lack of toxicity, and significant side effects support its application for long-term therapeutic use. In this review, we aim to recapitulate and discuss the effects, dosages, and administration routes of carnosine in preclinical in vivo models, with a particular focus on neurodegenerative disorders where it has been shown to reduce oxidative stress, suppress neuroinflammation, modulate protein aggregation, and preserve cognitive function, all key features of neurodegeneration. Despite promising findings, there are gaps in the knowledge on how carnosine affects synaptic plasticity, neuronal remodeling, and other processes that play a central role in the pathophysiology of neurodegenerative disorders. Additionally, clinical translation remains challenging due to inconsistencies across in vivo studies in terms of dosage, treatment duration, routes of administration, and disease models, which affect reproducibility and cross-study comparability. Therefore, while carnosine emerges as a multifunctional and well-tolerated molecule, further research is needed to clarify its therapeutic relevance in human diseases. In this review, we also address future perspectives and key methodological challenges that must be overcome to effectively translate carnosine's biological potential into clinical practice.