Peptides最新文献

{"title":"Endogenous opiates and behavior: 2024","authors":"Richard J. Bodnar","doi":"10.1016/j.peptides.2025.171422","DOIUrl":"10.1016/j.peptides.2025.171422","url":null,"abstract":"<div><div>This paper is the forty-seventh consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2024 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171422"},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurokinin B is a potential target for treating disruption of intestinal mucosal barrier in acute mechanical intestinal obstruction","authors":"Feifan Wang ,&nbsp;Xia Jiang ,&nbsp;Zifeng Zhao ,&nbsp;Yuanyuan Wang ,&nbsp;Haibo Jiang ,&nbsp;Yingchao Gao ,&nbsp;Haobo Wang ,&nbsp;Zhongxin Li","doi":"10.1016/j.peptides.2025.171419","DOIUrl":"10.1016/j.peptides.2025.171419","url":null,"abstract":"<div><h3>Background</h3><div>The neurokinin-B (NKB)/neurokinin-3-receptor (NK3R) pathway is involved in the inflammatory response. However, its role in the disruption of intestine mucosal barrier during mechanical intestinal obstruction (IO) remains unknown.</div></div><div><h3>Methods</h3><div>We collected serum samples from 30 mechanical IO patients and 30 healthy volunteers and measured the serum levels of NKB, lipopolysaccharide (LPS), diamine oxidase (DAO), and D‑lactate (D‑LA) by using ELISA. We subsequently used a mechanical IO mice model and intraperitoneally injected the mice with NKB (Senktide) and NK3R antagonist (NK3Ra). We used the ELISA to measure the tumor necrosis factor (TNF)-α, interleukin (IL)-6, LPS, DAO, and D-LA serum concentrations in the mice. Hematoxylin-eosin (H&amp;E) staining and transmission electron microscopy (TEM) were used to observe structural changes in the intestinal mucosa. Immunohistochemistry was used to detect the expression of claudin-1, occludin and ZO-1 in intestinal tissues.</div></div><div><h3>Results</h3><div>Serum NKB (75.36 ± 28.67 pg/mL <em>vs.</em> 44.95 ± 16.92 pg/mL) and LPS (7.38 ± 3.63 μg/mL <em>vs.</em> 4.50 ± 2.94 μg/mL) levels were higher in mechanical IO patients than in control people (<em>P</em> &lt; 0.05). We found a positive correlation between serum NKB and LPS levels in mechanical IO patients. The serum LPS concentration in the IO+NKB mice was greater than that in the IO mice (<em>P</em> = 0.001). After the use of NK3Ra, the serum LPS, DAO and D-LA levels decreased (<em>P</em> &lt; 0.05). H&amp;E staining indicated that the intestinal mucosal epithelial structure was severely damaged, including lamina propria hemorrhage, atrophied villi, and inflammatory cell infiltration in IO+NKB mice. TEM revealed that the junctional complexes between epithelial cells were disrupted and absent in the IO+NKB mice. Compared with those in the IO mice, the expression levels of claudin-1 and occludin in intestinal tissues were lower in the IO+NKB mice. However, the intraperitoneal injection of NK3Ra attenuated the damage to tight junction proteins and the intestinal mucosal structure caused by NKB. Additionally, we observed that the serum IL-6 and TNF-α levels in the IO+NK3Ra mice were lower than those in the IO mice (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>NKB might increase the levels of serum IL-6 and TNF-α by acting on the NK3 receptor, promoting intestinal inflammation, and subsequently destroying the intestinal mucosal barrier during mechanical IO.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171419"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole body distribution of the regulatory peptide 26RFa in male and female mice","authors":"Marie Picot ,&nbsp;Mélodie Devère ,&nbsp;Saloua Takhlidjt ,&nbsp;Corentin Guillemot ,&nbsp;Caroline Lusurier ,&nbsp;Gaëtan Prévost ,&nbsp;Nicolas Chartrel ,&nbsp;David Godefroy","doi":"10.1016/j.peptides.2025.171417","DOIUrl":"10.1016/j.peptides.2025.171417","url":null,"abstract":"<div><div>26RFa is a regulatory peptide initially isolated from the brain. 26RFa was found to be involved in the regulation of vital functions such as the regulation of energy and glucose metabolism. However, the whole distribution of 26RFa in the organs/tissues of the organism remains fragmentary although it represents a crucial step to discover novel physiological functions for this regulatory peptide. To this aim, we have generated a mouse line that expresses the fluorescent protein tdTomato in 26RFa-expressing cells, and visualization of tdTomato immunostaining <em>in toto</em> was performed using the tridimensional imaging approach.</div><div>Our observations reveal that 26RFa is largely distributed among the organism of male and female mice. 26RFa-expressing cells were notably found in numerous regions of the central nervous system including the olfactory bulbs, the cortex, the hippocampus, the hypothalamus, the cerebellum, the brainstem and the spinal cord. At the periphery, 26RFa-expressing structures were detected all along the gastrointestinal tract, in the liver, the white adipose tissue, the kidney, the adrenal gland, the lungs, the male and female reproductive tracts, the striated muscles, the thymus and a number of exocrine glands such as the salivary glands, the prostate, the seminal vesicles.</div><div>In conclusion, the present anatomical observations are in agreement with the main physiological functions previously reported for 26RFa such the regulation of energy and glucose metabolism or the control of the hypothalamo-pituitary-gonadal or adrenal axis. However, 26RFa is present in other organs/tissues in which its physiological relevance is totally unknown opening therefore a new field of research for this regulatory peptide.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171417"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF-1 contributes to cardiovascular protection in obesity by upregulating Na+/K+-ATPase activity and modulating key signaling pathways in rats on a high-fat diet","authors":"Katarina Banjac ,&nbsp;Milan Obradovic ,&nbsp;Sonja Zafirovic ,&nbsp;Esma R. Isenovic","doi":"10.1016/j.peptides.2025.171418","DOIUrl":"10.1016/j.peptides.2025.171418","url":null,"abstract":"<div><div>This study examined the ability of insulin-like growth factor-1 (IGF-1) to improve the expression and function of cardiac sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and reduce heart hypertrophy in obese rats. Adult male Wistar rats received a standard diet or a high-fat (HF) diet for 12 weeks. A bolus injection of IGF-1 (50 μg/kg, i.p.) was administered to half of the HF rats 24 hours before euthanasia. IGF-1 treatment increased: the activity of Na⁺/K⁺-ATPase and expression of phosphorylated and total Na⁺/K⁺-ATPase α₁ subunit, the phosphorylation of IGF-1 receptor β /insulin receptor β at Tyr¹¹³¹/Tyr¹¹⁴⁶, insulin receptor substrate-1 (IRS-1) at Tyr¹²²², mammalian target of rapamycin (mTOR) at Ser²⁴⁸¹, protein kinase B (Akt) at Ser⁴⁷³ and the expression of type-2 angiotensin II <em>(</em>AngII) receptor (AT₂R). Conversely, IGF-1 reduced the levels of IRS-1 phosphorylated at Ser³⁰⁷, mTOR at Ser²⁴⁴⁸, ribosomal protein p70 S6 kinase (S6K) at Thr⁴²¹/Ser⁴²⁴, and the expression of type-1 Ang II receptor (AT₁R) in the heart, as well as the serum levels of Ang II in obese rats. IGF-1 treatment reduced cardiac mass and elevated mRNA expression of the α-myosin heavy chain (MHC), and the α/β MHC ratio in the hearts of obese rats. The results of this study suggest that the administration of IGF-1 to obese rats reduces the adverse effects of HF diet, potentially by lowering Ang II-mediated activation of mTOR/S6K and enhancing the IRS-1/Akt pathway, which promotes Na⁺/K⁺-ATPase activity in the heart and diminishes cardiac hypertrophy.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171418"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spexin is a biomarker of the process that regulates leptin sensitivity","authors":"Mohamed Badie Ahmed ,&nbsp;Abdella M. Habib ,&nbsp;Saif Badran ,&nbsp;Abeer Alsherawi ,&nbsp;Asma Syed ,&nbsp;Hoda Khoogaly ,&nbsp;Atalla Hammouda ,&nbsp;Abdul-Badi Abou-Samra ,&nbsp;Suhail A. Doi","doi":"10.1016/j.peptides.2025.171416","DOIUrl":"10.1016/j.peptides.2025.171416","url":null,"abstract":"<div><div>The rising prevalence of obesity poses a critical threat to global health, prompting an urgent need for a comprehensive understanding of its underlying mechanisms. This study aimed to delve into the relationship between obesity, leptin sensitivity, and gut hormones, focusing on spexin, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP). We examined patients undergoing body contouring surgeries to assess how these hormones and leptin interact. Blood samples were collected at three different time points, and hormone levels were analyzed. Our findings indicated that increases in GLP-1 and decreases in GIP correlated with improved leptin sensitivity, indicated by decreased plasma leptin levels and associated with increase in steepness of the plasma leptin-spexin slope. These results suggest that spexin may serve as a biomarker for leptin sensitivity, the latter influenced by gut hormones in obese individuals. The study provides further evidence that the modulation of leptin sensitivity by gut hormones could be key in addressing obesity and its metabolic consequences.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171416"},"PeriodicalIF":2.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma angiotensinogen is associated with higher 24-hour ambulatory blood pressure independently of plasma angiotensin II in obese men","authors":"Camilla L. Asferg ,&nbsp;Ulrik B. Andersen ,&nbsp;Jørgen L. Jeppesen","doi":"10.1016/j.peptides.2025.171410","DOIUrl":"10.1016/j.peptides.2025.171410","url":null,"abstract":"<div><div>The introduction of liver-targeted antisense oligonucleotides and small interfering ribonucleic acids that inhibit hepatic angiotensinogen synthesis has led to renewed interest in the role of angiotensinogen in hypertension. Therefore, we decided to do further angiotensinogen analyses in a hypertension research program, where we found that obese hypertensive men, given their high salt intake and high 24-hour ambulatory blood pressure (ABP), had higher than expected renin-angiotensin-system (RAS) activity. In a cross-sectional study, we examined 64 newly diagnosed treatment-naïve obese hypertension men (body mass index (BMI) ≥ 30 kg/m², 24-hour systolic ABP ≥ 130 mm Hg and/or 24-hour diastolic ABP ≥ 80 mm Hg), and 40 obese normotensive men (BMI ≥30 mg/m², 24-hour systolic ABP &lt;130 and 24-hour diastolic ABP &lt;80 mm Hg). Blood for biochemical evaluation of the RAS was drawn after 60 minutes rest in the supine position. We applied multiple linear regression analysis to explore independent associations. The obese hypertensive men had a higher mean fasting plasma concentration of angiotensinogen than the obese normotensive men (970.4 ± 214.3 nmol/L versus 868.4 ± 173.0 nmol/L, <em>P</em> = 0.013). Adjusted for age and angiotensin II, angiotensinogen was significantly associated with 24-hour systolic ABP (regression coefficient±standard error (mm Hg/100 nmol/L angiotensinogen): 1.8 ± 0.6, <em>P</em> = 0.006), 24-hour diastolic ABP (0.8 ± 0.3, <em>P</em> = 0.021), and 24-hour pulse pressure (1.0 ± 0.4, <em>P</em> = 0.028). Thus, plasma angiotensinogen was associated with higher 24-hour ABPs independently of plasma angiotensin II in obese men. However, further studies are warranted to determine whether angiotensinogen is only a risk marker of high BP or has BP raising effects independent of angiotensin II.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171410"},"PeriodicalIF":2.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of galanin receptors 2 and 3 double-knockout on neuroinflammation and functional recovery following traumatic brain injury","authors":"Susanne M. Brunner ,&nbsp;Stefanie Gaisbauer ,&nbsp;Patrick N. Pallier ,&nbsp;Ping K. Yip ,&nbsp;Andrea Ramspacher ,&nbsp;Julia Leitner ,&nbsp;Felix Sternberg ,&nbsp;Christina Erhardt-Kreutzer ,&nbsp;Theresa Haslauer ,&nbsp;Sara Huber ,&nbsp;Lara Bieler ,&nbsp;Sebastien Couillard-Despres ,&nbsp;Barbara Kofler","doi":"10.1016/j.peptides.2025.171415","DOIUrl":"10.1016/j.peptides.2025.171415","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is one of the world’s leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL_1–3R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL₂R and GAL₃R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL_2/3R-double-KO (GAL_2/3R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1–28 post injury), neurological dysfunction was more severe in GAL_2/3R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL_2/3R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL₂R and/or GAL₃R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171415"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PACAP inhibits sepsis-associated acute lung injury by inhibiting the Sp1/AQP1 pathway","authors":"Zhuangzhi Xiong ,&nbsp;Xiaoqin Zhou ,&nbsp;Yufeng Li ,&nbsp;Liu Yang","doi":"10.1016/j.peptides.2025.171411","DOIUrl":"10.1016/j.peptides.2025.171411","url":null,"abstract":"<div><div>Sepsis-induced acute lung injury (ALI) represents a severe pathological state marked by uncontrolled inflammation, redox imbalance, and alveolar-capillary barrier breakdown. Here, we evaluated the therapeutic potential of pituitary adenylate cyclase-activating polypeptide (PACAP) in a murine sepsis-ALI model. PACAP treatment notably ameliorated histological damage, reduced oxidative stress biomarkers, and mitigated inflammatory processes, including neutrophil accumulation and pro-inflammatory cytokine release. Molecular analysis revealed PACAP-mediated downregulation of Aquaporin-1 (AQP1) and specificity protein 1 (Sp1), key regulators of alveolar fluid homeostasis and inflammatory signaling. Genetic Sp1 overexpression abrogated PACAP-induced AQP1 suppression, validating the Sp1/AQP1 signaling pathway as a critical mediator of PACAP’s protective effects. Additionally, in vitro MTT assays on RAW 264.7 macrophages demonstrated that PACAP has low toxicity at biologically relevant levels. These findings demonstrate PACAP’s therapeutic promise for sepsis-ALI through modulation of the Sp1/AQP1 axis.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171411"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effects of peripherally administered nicotine on food intake via the central anorectic peptide nesfatin-1/nucleobindin-2 in adult male rats","authors":"Reiko Saito ,&nbsp;Yukiyo Yamamoto ,&nbsp;Reiji Fukano ,&nbsp;Masatomo Mori ,&nbsp;Takashi Maruyama ,&nbsp;Yoichi Ueta","doi":"10.1016/j.peptides.2025.171409","DOIUrl":"10.1016/j.peptides.2025.171409","url":null,"abstract":"<div><div>Acute/chronic exposure to nicotine modulates feeding behavior in experimental animals and humans. However, how nicotine modulates food intake remains unclear. This study examined the acute effects of the peripheral administration of nicotine on food intake in adult male rats, focusing on the possible involvement of the anorectic peptide nesfatin-1/nucleobindin-2 (NucB2) in the central nervous system (CNS). Initially, cumulative food intake, but not water intake, was significantly decreased 0.5, 1, and 1.5 h after the intraperitoneal administration of nicotine (0.5 mg/kg) in 24h-fasted rats. Subsequently, the double-labeled immunohistochemical study revealed that nesfatin-1/NucB2-immunoreactive (ir) neurons expressed Fos-ir in various nuclei of the hypothalamic and brainstem areas, including the supraoptic nucleus and ventral tegmental areas, 90 min after the intraperitoneal administration of nicotine. Finally, pretreatment with intracerebroventricular administration of antisense RNA against nesfatin-1/NucB2 significantly attenuated the suppression of food intake induced by intraperitoneal nicotine administration. The results indicated that the acute effects of peripherally administered nicotine on the suppression of food intake may be partially involved in nesfatin-1/NucB2-containing neurons in the CNS in male adult rats.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"189 ","pages":"Article 171409"},"PeriodicalIF":2.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide therapeutics: current status and future opportunity with focus on nose-to-brain delivery☆","authors":"Eva-Maria Jülke,&nbsp;Annette G. Beck-Sickinger","doi":"10.1016/j.peptides.2025.171404","DOIUrl":"10.1016/j.peptides.2025.171404","url":null,"abstract":"<div><div>Peptide drugs are a highly diverse group of therapeutic agents. Over the last decade, more than 40 peptides have been approved for clinical use. They target different structures, ranging from G protein-coupled receptors (GPCRs) to pathogens and are used to treat a variety of indications, including metabolic disorders, genetic diseases, acute illnesses and more. Structurally, peptide therapeutics are a heterogeneous class. This diversity allows them to bridge the gap between small molecules and biologics. However, limited metabolic stability and bioavailability must be addressed. Strategies to improve the half-life include backbone and sequence modification, cyclization and the addition of stabilizing moieties. Great strides have been made in recent years towards achieving sufficient drug uptake for oral application have been achieved within recent years. However, these methods require specialized peptide design or involve permeabilization of the gastrointestinal tract. Consequently, other routes of administration are being explored. One promising approach is the nasal application of peptides. This method can be used for systemic uptake, but also allows for direct nose-to-brain delivery of compounds. While successful nose-to-brain delivery is already used in the clinic, the underlining mechanisms are poorly understood. Strategies for rational optimization are needed to make this method more applicable to a wider range of compounds. Overall, approved peptide therapeutics cover a wide range of applications and have demonstrated a growing and novel potential in recent drug discovery.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171404"},"PeriodicalIF":2.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}