PeptidesPub Date : 2024-02-28DOI: 10.1016/j.peptides.2024.171183
Liuqing Xi , Juan Du , Wen Xue , Kan Shao , Xiaohong Jiang , Wenfang Peng , Wenyi Li , Shan Huang
{"title":"Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy","authors":"Liuqing Xi , Juan Du , Wen Xue , Kan Shao , Xiaohong Jiang , Wenfang Peng , Wenyi Li , Shan Huang","doi":"10.1016/j.peptides.2024.171183","DOIUrl":"10.1016/j.peptides.2024.171183","url":null,"abstract":"<div><p>Diabetic patients often experience impaired wound healing. Human cathelicidin LL-37 possesses various biological functions, such as anti-microbial, anti-inflammatory, and pro-wound healing activities. Autophagy has important effects on skin wound healing. However, little is known about whether LL-37 accelerates diabetic wound healing by regulating autophagy. In the study, we aimed to investigate the role of autophagy in LL-37-induced wound healing and uncover the underlying mechanisms involved. A full-thickness wound closure model was established in diabetic mice to evaluate the effects of LL-37 and an autophagy inhibitor (3-MA) on wound healing. The roles of LL-37 and 3-MA in regulating keratinocyte migration were assessed using transwell migration and wound healing assays. The activation of transcription factor EB (TFEB) was measured using western blotting and immunofluorescence (IF) assays of its nuclear translocation. The results showed that LL-37 treatment improved wound healing in diabetic mice, whereas these effects were reversed by 3-MA. <em>In vitro</em>, 3-MA decreased the effects of LL-37 on promoting HaCat keratinocyte migration in the presence of high glucose (HG). Mechanistically, LL-37 promoted TFEB activation and resulted in subsequent activation of autophagy, as evidenced by increased nuclear translocation of TFEB and increased expression of ATG5, ATG7, and beclin 1 (BECN1), whereas these changes were blocked by TFEB knockdown. As expected, TFEB knockdown damaged the effects of LL-37 on promoting keratinocyte migration. Collectively, these results suggest that LL-37 accelerates wound healing in diabetic mice by activating TFEB-dependent autophagy, providing new insights into the mechanism by which LL-37 promotes diabetic wound healing.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171183"},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996990","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}
PeptidesPub Date : 2024-02-28DOI: 10.1016/j.peptides.2024.171182
Eduardo Nocchi , Sérgio Scalzo , Cibele Rocha-Resende , Pedro Almeida , Amanda Parreira , Kiany Miranda , Victor Moura , Robson A.S. dos Santos , Silvia Guatimosim
{"title":"The Mas agonist CGEN-856S prevents Ang II induced cardiomyocyte hypertrophy via nitric oxide production","authors":"Eduardo Nocchi , Sérgio Scalzo , Cibele Rocha-Resende , Pedro Almeida , Amanda Parreira , Kiany Miranda , Victor Moura , Robson A.S. dos Santos , Silvia Guatimosim","doi":"10.1016/j.peptides.2024.171182","DOIUrl":"10.1016/j.peptides.2024.171182","url":null,"abstract":"<div><p>With the previous knowledge of the cardioprotective effects of the Angiotensin-(1−7) axis, a agonist of Mas receptor has been described, the CGEN-856S. This peptide is more stable than Ang-(1−7), and has a low binding affinity to Angiotensin II receptors. Although the cardioprotective effects of CGEN-856S were previously shown <em>in vivo,</em> the mechanisms behind its effects are still unknown. Here, we employed a combination of molecular biology, confocal microscopy, and genetically modified mouse with Mas deletion to investigate the CGEN-856S protective signaling in cardiomyocytes. In isolated adult ventricular myocytes, CGEN-856S induced an increase in nitric oxide (NO) production which was absent in cells from Mas knockout mice. Using western blot, we observed a significant increase in phosphorylation of AKT after treatment with CGEN-856S. In addition, CGEN-856S prevented the Ang II induced hypertrophy and the nuclear translocation of GRK5 in a culture model of rat neonatal cardiomyocytes. Blockage of Mas receptor and inhibition of the NO synthase abolished the effects of CGEN-856S on Ang II treated cardiomyocytes. In conclusion, we show that CGEN-856S acting via receptor Mas induces NO raise to block Ang II induced cardiomyocyte hypertrophy. These results indicate that CGEN-856S acts very similarly to Ang-(1−7) in cardiac myocytes, highlighting its therapeutic potential for treating cardiovascular diseases.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171182"},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013126","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}
PeptidesPub Date : 2024-02-27DOI: 10.1016/j.peptides.2024.171181
Muriel Larauche, Yong Sung Kim , Agata Mulak , Henri Duboc , Yvette Taché
{"title":"Intracerebroventricular administration of TRH Agonist, RX-77368 alleviates visceral pain induced by colorectal distension in rats","authors":"Muriel Larauche, Yong Sung Kim , Agata Mulak , Henri Duboc , Yvette Taché","doi":"10.1016/j.peptides.2024.171181","DOIUrl":"10.1016/j.peptides.2024.171181","url":null,"abstract":"<div><p>Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100 ng/rat) or saline (5 µl) or were semi-restrained and exposed to cold (4°C) for 45 min. The visceromotor response (VMR) to graded phasic colorectal distensions (CRD) was monitored using non-invasive intracolonic pressure manometry. Naloxone (1 mg/kg) was injected subcutaneously 10 min before ICV RX-77368 or saline. Fecal pellet output was monitored for 1 h after ICV injection. RX-77368 ICV (10, 30 and 100 ng/rat) reduced significantly the VMR by 56.7%, 67.1% and 81.1% at 40 mmHg and by 30.3%, 58.9% and 87.4% at 60 mmHg respectively vs ICV saline. Naloxone reduced RX-77368 (30 and 100 ng, ICV) analgesic response by 51% and 28% at 40 mmHg and by 30% and 33% at 60 mmHg respectively, but had no effect per se. The visceral analgesia was mimicked by the acute exposure to cold. At the doses of 30 and 100 ng, ICV RX-77368 induced defecation within 30 min. These data established the antinociceptive action of RX-77368 injected ICV in a model of visceral pain induced by colonic distension through recruitment of both opioid and non-opioid dependent mechanisms.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171181"},"PeriodicalIF":3.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000342/pdfft?md5=58324a4a76471a875348aa9720a9cbfa&pid=1-s2.0-S0196978124000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PeptidesPub Date : 2024-02-22DOI: 10.1016/j.peptides.2024.171180
J. Michael Conlon, Bosede O. Owolabi, Peter R. Flatt, Yasser H.A. Abdel-Wahab
{"title":"Amphibian host-defense peptides with potential for Type 2 diabetes therapy – an updated review","authors":"J. Michael Conlon, Bosede O. Owolabi, Peter R. Flatt, Yasser H.A. Abdel-Wahab","doi":"10.1016/j.peptides.2024.171180","DOIUrl":"10.1016/j.peptides.2024.171180","url":null,"abstract":"<div><p>Investigations conducted since 2018 have identified several host-defense peptides present in frog skin secretions whose properties suggest the possibility of their development into a new class of agent for Type 2 diabetes (T2D) therapy. Studies <em>in vitro</em> have described peptides that (a) stimulate insulin release from BRIN-BD11 clonal β-cells and isolated mouse islets, (b) display β-cell proliferative activity and protect against cytokine-mediated apoptosis and (c) stimulate production of the anti-inflammatory cytokine IL-10 and inhibit production of the pro-inflammatory cytokines TNF-α and IL-1β. Rhinophrynin-27, phylloseptin-3.2TR and temporin F are peptides with therapeutic potential. Studies <em>in vivo</em> carried out in <em>db/db</em> and high fat-fed mice have shown that twice-daily administration of [S4K]CPF-AM1 and [A14K]PGLa-AM1, analogs of peptides first isolated from the octoploid frog <em>Xenopus amieti</em>, over 28 days lowers circulating glucose and HbA1c concentrations, increases insulin sensitivity and improves glucose tolerance and lipid profile. Peptide treatment produced potentially beneficial changes in the expression of skeletal muscle genes involved in insulin signaling and islet genes involved in insulin secretion in these murine models of T2D. Lead compounds uncovered by the study of frog HDPs may provide a basis for the design of new types of agents that can be used, alone or in combination with existing therapies, for the treatment of T2D.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171180"},"PeriodicalIF":3.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000330/pdfft?md5=a48b654362a742af45c89cc08e4d4406&pid=1-s2.0-S0196978124000330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior","authors":"Hiroyuki Arakawa , Mana Tokashiki , Yuki Higuchi , Toshihiro Konno","doi":"10.1016/j.peptides.2024.171178","DOIUrl":"10.1016/j.peptides.2024.171178","url":null,"abstract":"<div><p>Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171178"},"PeriodicalIF":3.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773916","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}
PeptidesPub Date : 2024-02-14DOI: 10.1016/j.peptides.2024.171179
Ali H. Shilleh , Katrina Viloria , Johannes Broichhagen , Jonathan E. Campbell , David J. Hodson
{"title":"GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells","authors":"Ali H. Shilleh , Katrina Viloria , Johannes Broichhagen , Jonathan E. Campbell , David J. Hodson","doi":"10.1016/j.peptides.2024.171179","DOIUrl":"10.1016/j.peptides.2024.171179","url":null,"abstract":"<div><p>Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are transmembrane receptors involved in insulin, glucagon and somatostatin secretion from the pancreatic islet. Therapeutic targeting of GLP1R and GIPR restores blood glucose levels in part by influencing beta cell, alpha cell and delta cell function. Despite the importance of the incretin-mimetics for diabetes therapy, our understanding of GLP1R and GIPR expression patterns and signaling within the islet remain incomplete. Here, we present the evidence for GLP1R and GIPR expression in the major islet cell types, before addressing signaling pathway(s) engaged, as well as their influence on cell survival and function. While GLP1R is largely a beta cell-specific marker within the islet, GIPR is expressed in alpha cells, beta cells, and (possibly) delta cells. GLP1R and GIPR engage G<sub>s</sub>-coupled pathways in most settings, although the exact outcome on hormone release depends on paracrine communication and promiscuous signaling. Biased agonism away from beta-arrestin is an emerging concept for improving therapeutic efficacy, and is also relevant for GLP1R/GIPR dual agonism. Lastly, dual agonists exert multiple effects on islet function through GIPR > GLP1R imbalance, increased GLP1R surface expression and cAMP signaling, as well as beneficial alpha cell-beta cell-delta cell crosstalk.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171179"},"PeriodicalIF":3.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000329/pdfft?md5=6f72256f5ca9449c0e77674156c82450&pid=1-s2.0-S0196978124000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PeptidesPub Date : 2024-02-12DOI: 10.1016/j.peptides.2024.171177
Kuiming Zou , Shaojie Zhang , Kedong Yin , Shiming Ren , Mengjun Zhang , Xiatong Li , Lixin Fan , Ruiling Zhang , Ruifang Li
{"title":"Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes","authors":"Kuiming Zou , Shaojie Zhang , Kedong Yin , Shiming Ren , Mengjun Zhang , Xiatong Li , Lixin Fan , Ruiling Zhang , Ruifang Li","doi":"10.1016/j.peptides.2024.171177","DOIUrl":"10.1016/j.peptides.2024.171177","url":null,"abstract":"<div><p><em>Trichophyton mentagrophytes</em> is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of <em>T. mentagrophytes</em>. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against <em>T. mentagrophytes</em> than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited <em>T. mentagrophytes</em> spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in <em>T. mentagrophytes</em>. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of <em>T. mentagrophytes</em> from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171177"},"PeriodicalIF":3.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735814","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":"In silico and in vivo experiment of soymilk peptide (tetrapeptide - FFYY) for the treatment of hypertension","authors":"Md Alauddin , Md. Ruhul Amin , Muhammad Ali Siddiquee , Kazuyuki Hiwatashi , Atsushi Shimakage , Saori Takahashi , Mamoru Shinbo , Michio Komai , Hitoshi Shirakawa","doi":"10.1016/j.peptides.2024.171170","DOIUrl":"10.1016/j.peptides.2024.171170","url":null,"abstract":"<div><p>Enzyme-Treated Soymilk (ETS) was produced from Commercial Soymilk (CSM) with the treatment of proteinase PROTIN SD-NY10 (<em>Bacillus amyloliquefaciens)</em>. Previously, we have isolated novel peptides from ETS but data related to isolated-peptides are scant. In this study, bio-informatics and in vivo analysis of isolated-peptides showed strong binding affinity to the active site of the Angiotensin Converting Enzyme (ACE). Among four peptides, tetrapeptide Phe-Phe-Tyr-Tyr (FFYY) showed strong binding affinity and inhibitory activity to the ACE-enzyme (binding affinity −9.5 Kcal/mol and inhibitory concentration of 1.9 µM respectively) as well as showed less toxicity compared to other peptides. The animal experiment revealed that single oral dose of FFYY (80 µg/kg body weight/day) effectively ameliorates the systolic, diastolic and mean blood pressure in the spontaneously hypertensive rat (SHR) model. Chronic oral administration of FFYY (80 µg/kg body weight/day for 3 weeks) reduced the systolic blood pressure elevation and ACE activity without any adverse side effects on the physiological and biological parameters of SHR. In conclusion, both <em>in silico</em> and in vivo experiments of soymilk-isolated FFYY peptide showed a promising option as a potential alternative for hypertension treatment without adverse side effects on SHR.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171170"},"PeriodicalIF":3.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717790","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}
PeptidesPub Date : 2024-02-09DOI: 10.1016/j.peptides.2024.171169
Dávid Vörös , Orsolya Kiss , Márton Taigiszer , Bettina Réka László , Tamás Ollmann , László Péczely , Olga Zagorácz , Erika Kertes , Veronika Kállai , Beáta Berta , Anita Kovács , Zoltán Karádi , László Lénárd , Kristóf László
{"title":"The role of intraamygdaloid oxytocin in spatial learning and avoidance learning","authors":"Dávid Vörös , Orsolya Kiss , Márton Taigiszer , Bettina Réka László , Tamás Ollmann , László Péczely , Olga Zagorácz , Erika Kertes , Veronika Kállai , Beáta Berta , Anita Kovács , Zoltán Karádi , László Lénárd , Kristóf László","doi":"10.1016/j.peptides.2024.171169","DOIUrl":"10.1016/j.peptides.2024.171169","url":null,"abstract":"<div><p>The goal of the present study is to investigate the role of intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin is a neuropeptide which is involved in social bonding, trust, emotional responses and various social behaviors. By conducting passive avoidance and Morris water maze tests on male Wistar rats, the role of intraamygdaloid oxytocin in memory performance and learning was investigated. Oxytocin doses of 10 ng and 100 ng were injected into the central nucleus of the amygdala. Our results showed that 10 ng oxytocin significantly reduced the time required to locate the platform during the Morris water maze test while significantly increasing the latency time in the passive avoidance test. However, the 100 ng oxytocin experiment failed to produce a significant effect in either of the tests. Wistar rats pretreated with 20 ng oxytocin receptor antagonist (L-2540) were administered 10 ng of oxytocin into the central nucleus of the amygdala and were also subjected to the aforementioned tests to highlight the role of oxytocin receptors in spatial- and avoidance learning. Results suggest that oxytocin supports memory processing during both the passive avoidance and the Morris water maze tests. Oxytocin antagonists can however block the effects of oxytocin in both tests. The results substantiate that oxytocin uses oxytocin receptors to enhance memory and learning performance.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171169"},"PeriodicalIF":3.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000226/pdfft?md5=03db660165821b84f3b1547508ad427b&pid=1-s2.0-S0196978124000226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PeptidesPub Date : 2024-02-06DOI: 10.1016/j.peptides.2024.171167
Kamini R. Shirsath , Vaishnavi K. Patil , Sanjay N. Awathale, Sameer N. Goyal, Kartik T. Nakhate
{"title":"Pathophysiological and therapeutic implications of neuropeptide S system in neurological disorders","authors":"Kamini R. Shirsath , Vaishnavi K. Patil , Sanjay N. Awathale, Sameer N. Goyal, Kartik T. Nakhate","doi":"10.1016/j.peptides.2024.171167","DOIUrl":"10.1016/j.peptides.2024.171167","url":null,"abstract":"<div><p>Neuropeptide S (NPS) is a 20 amino acids-containing neuroactive molecule discovered by the reverse pharmacology method. NPS is detected in specific brain regions like the brainstem, amygdala, and hypothalamus, while its receptor (NPSR) is ubiquitously expressed in the central nervous system (CNS). Besides CNS, NPS and NPSR are also expressed in the peripheral nervous system. NPSR is a G-protein coupled receptor that primarily uses Gq and Gs signaling pathways to mediate the actions of NPS. In animal models of Parkinsonism and Alzheimer’s disease, NPS exerts neuroprotective effects. NPS suppresses oxidative stress, anxiety, food intake, and pain, and promotes arousal. NPSR facilitates reward, reinforcement, and addiction-related behaviors. Genetic variation and single nucleotide polymorphism in NPSR are associated with depression, schizophrenia, rheumatoid arthritis, and asthma. NPS interacts with several neurotransmitters including glutamate, noradrenaline, serotonin, corticotropin-releasing factor, and gamma-aminobutyric acid. It also modulates the immune system via augmenting pro-inflammatory cytokines and plays an important role in the pathogenesis of rheumatoid arthritis and asthma. In the present review, we discussed the distribution profile of NPS and NPSR, signaling pathways, and their importance in the pathophysiology of various neurological disorders. We have also proposed the areas where further investigations on the NPS system are warranted.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171167"},"PeriodicalIF":3.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703038","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}