Neuropeptides最新文献

{"title":"Research progress on the protection and mechanism of active peptides in Alzheimer's disease and Parkinson's disease","authors":"","doi":"10.1016/j.npep.2024.102457","DOIUrl":"10.1016/j.npep.2024.102457","url":null,"abstract":"<div><p>Neurodegenerative diseases are the main causes of death and morbidity among elderly people worldwide. From the pathological point of view, oxidative stress, neuroinflammation, mitochondrial damage and apoptosis are the causes of neuronal diseases, and play a harmful role in the process of neuronal cell death and neurodegeneration. The most common neurodegenerative diseases are Alzheimer's disease(AD) and Parkinson's disease(PD), and there is no effective treatment. The physiological role of active peptides in the human body is significant. Modern medical research has found that animal and plant peptides, natural peptides in human body, can act on the central nervous system, and their active components can improve learning and memory ability, and play the roles of antioxidation, anti-inflammation, anti-apoptosis and maintaining the structure and function of mitochondria. This review reviews the reports on neurodegenerative diseases such as AD and PD by active peptides from animals and plants and natural peptides from the human body, and summarizes the neuroprotective mechanism of peptides. A theoretical basis for further research and development of active peptides was provided by examining the research and application of peptides, which provided a theoretical basis for further research and development.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish","authors":"","doi":"10.1016/j.npep.2024.102456","DOIUrl":"10.1016/j.npep.2024.102456","url":null,"abstract":"<div><p>Prokineticin 2 (PK2) binds to prokineticin receptor 1 and prokineticin receptor 2 (PKR1 and PKR2, respectively), two G protein-coupled receptors (GPCRs) that can mediate multiple signalling pathways by promoting the elevation of intracellular calcium and cAMP levels, phosphorylation of Akt and activation of ERK and STAT3. This work aims to evidence the conservation of protein sequence and the mechanism of PK2 binding to PKR1 to use the zebrafish model for the identification of new drugs as targets of prokineticin receptors. To this end, we first demonstrated that the zebrafish genes <em>pk2</em> and <em>pkr1</em> are phylogenetically related to orthologous mammalian genes by constructing evolutionary trees and performing syntenic analyses. Subsequently, by comparing the amino acid sequences, we showed that the interaction sites with PK2 are conserved in the zPKR1. Using GST pull-down and cross-linking experiments, we demonstrated the crucial role of the N-terminal region of zPKR1 for binding to the PK2. Finally, by expressing zPKR1 in CHO cells, we demonstrated the ability of zPKR1 to induce the activation of ERK and STAT3.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bromelain decreases oxidative stress and Neuroinflammation and improves motor function in adult male rats with cerebellar Ataxia induced by 3-acetylpyridine","authors":"","doi":"10.1016/j.npep.2024.102455","DOIUrl":"10.1016/j.npep.2024.102455","url":null,"abstract":"<div><p>Bromelain is a plant-based molecule with antioxidant, antithrombotic, anticancer, and anti-inflammatory properties. Bromelain has been shown to reduce the release of inflammatory cytokines. This study aimed to determine whether bromelain can prevent ataxia in rats caused by 3-acetylpyridine (3-AP). Thirty-six albino rats were divided into the control, 3-AP, and 3-AP + Brom groups. In the 3-AP + Brom group, bromelain was injected intraperitoneally at 40 mg/kg daily for 30 days. Various techniques such as rotarod, electromyography (EMG), elevated plus maze, IHC, and Sholl analysis were used to evaluate the possible effects of bromelain on cerebellar neurons and glial cells. The results demonstrated significant improvements in most of the 3-AP + Brom, including motor coordination, neuromuscular response, anxiety, oxidative capacity, microgliosis, astrogliosis, cell death, and morphological variables compared to the 3-AP group. The mechanism of action of bromelain in restoring cerebellar ataxia needs further investigation, but it may be a candidate to help restore degeneration in animals with ataxia.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic activation ofarcuate nucleus NPY and NPY/AgRP neurons increases feeding behaviour in mice","authors":"Neda Rafiei ,&nbsp;Caitlin S. Mitchell ,&nbsp;Caitlin R. Tedesco ,&nbsp;Jessica Chen ,&nbsp;Eun A. Choi ,&nbsp;Stephanie Roughley ,&nbsp;Philip Jean-Richard-dit-Bressel ,&nbsp;Natasha N. Kumar ,&nbsp;Gavan P. McNally ,&nbsp;Herbert Herzog ,&nbsp;Denovan P. Begg","doi":"10.1016/j.npep.2024.102454","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102454","url":null,"abstract":"<div><p>Neuropeptide Y (NPY) plays a crucial role in controlling energy homeostasis and feeding behaviour. The role of NPY neurons located in the arcuate nucleus of the hypothalamus (Arc) in responding to homeostatic signals has been the focus of much investigation, but most studies have used AgRP promoter-driven models, which do not fully encompass Arc NPY neurons. To directly investigate NPY-expressing versus AgRP-expressing Arc neurons function, we utilised chemogenetic techniques in NPY-Cre and AgRP-Cre animals to activate Arc NPY or AgRP neurons in the presence of food and food-related stimuli. Our findings suggest that chemogenetic activation of the broader population of Arc NPY neurons, including AgRP-positive and AgRP-negative NPY neurons, has equivalent effects on feeding behaviour as activation of Arc AgRP neurons. Our results demonstrate that these Arc NPY neurons respond specifically to caloric signals and do not respond to non-caloric signals, in line with what has been observed in AgRP neurons. Activating Arc NPY neurons significantly increases food consumption and influences macronutrient selection to prefer fat intake.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141543415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute sleep deprivation (ASD) and cardioprotection: Impact of ASD on oxytocin-mediated sympathetic nervous activation preceding myocardial infarction","authors":"Marjan Aghajani ,&nbsp;Mozhgan Aghajani ,&nbsp;Ehsan Kazemi Moghaddam ,&nbsp;Mahdieh Faghihi ,&nbsp;Alireza Imani","doi":"10.1016/j.npep.2024.102453","DOIUrl":"10.1016/j.npep.2024.102453","url":null,"abstract":"<div><h3>Introduction</h3><p>This study explored how acute sleep deprivation (ASD) before myocardial ischemia influences oxytocin release from paraventricular (PVN) neurons and its correlation with sympathetic nervous system (SNS) activity post-acute sleep loss, impacting subsequent left ventricular (LV) remodeling following myocardial infarction (MI).</p></div><div><h3>Methods</h3><p>The study was conducted in two phases: induction of ASD, inducing MI, blood sampling, euthanizing animals and collecting their heart and brain for histological and gene expression evaluations. The animals in first and second phase were euthanized 24 h and 14 days after MI, respectively.</p></div><div><h3>Results</h3><p>Pre-MI ASD, accompanied by increased serum epinephrine levels within 24 h of MI, upregulated oxytocin and cFos expression in the PVN. Also, pre-MI ASD resulted in decreased serum PAB levels 14 days post-MI (<em>P</em> &lt; 0.001). While notable echocardiographic changes were seen in MI versus sham groups, ASD demonstrated protective effects. This was evidenced by reduced infarct size, elevated TIMP1, MMP2, and MMP9 in the LV of SD + MI animals versus MI alone (<em>P</em> &lt; 0.05). Additionally, histological analysis showed reduced LV fibrosis in pre-MI ASD subjects (P &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>Our study supports the notion that activation of oxytocin neurons within the PVN subsequent to ASD interacts with autonomic centers in the central nervous system. This enhanced sympathetic outflow to the heart prior to MI triggers a preconditioning response, thereby mediating cardioprotection through decreased oxidative stress biomarkers and regulated extracellular matrix (ECM) turnover.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liangxue Tongyu prescription attenuates neuroinflammation by increasing cholecystokinin octapeptide in acute intracerebral hemorrhage rats","authors":"Jianxiang Li ,&nbsp;Yingying Sun ,&nbsp;Wenzhe Qiu ,&nbsp;Yu Zhou ,&nbsp;Dandan Zhou ,&nbsp;Yang Zhao ,&nbsp;Anlan Liu ,&nbsp;Yuan Yuan ,&nbsp;Weifeng Guo","doi":"10.1016/j.npep.2024.102452","DOIUrl":"10.1016/j.npep.2024.102452","url":null,"abstract":"<div><p>Inflammatory reactions after acute intracerebral hemorrhage (AICH) contribute significantly to a poor prognosis. Liangxue Tongyu Prescription (LTP) has been proven to be clinically effective in treating AICH. Numerous studies have shown that LTP suppresses brain inflammatory damage in AICH, while the internal mechanisms underlying its action remain unclear. The aim of this study was to verify the anti-inflammatory effects of LTP on an AICH rat model and investigate the potential mechanisms. The AICH rat models were created by injecting autologous blood into the right caudate nucleus. LTP markedly decreased cerebral hematoma and brain water content and recovered from neurological deficits. Meanwhile, LTP prevented microglial activation and reduced the inflammatory reaction caused by pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Notably, the expression of cholecystokinin octapeptide (CCK-8) in the brain and intestine was increased by LTP or CCK-8 treatment. LTP further suppressed nuclear factor kappa B (NF-κB) in the brains of rats with AICH. Moreover, LTP increased the protein and mRNA expression of Occludin and Claudin-1 in the intestine and decreased the levels of lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum. Furthermore, the results showed that LTP increased the protein and mRNA expression of Claudin-5 and zonula occludens-1 (ZO-1) in the brain. CCK-8 receptor antagonists increased the expression of NF-κB and the concentration of pro-inflammatory cytokines. These findings suggested that LTP attenuated neuroinflammation by increasing CCK-8 in the brain and intestine, and its mechanism might be related to alterations in the gut-brain axis (GBA).</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bezafibrate protects blood-brain barrier (BBB) integrity against traumatic brain injury mediated by AMPK","authors":"","doi":"10.1016/j.npep.2024.102450","DOIUrl":"10.1016/j.npep.2024.102450","url":null,"abstract":"<div><p>Bezafibrate (BEZ) has displayed a wide range of neuroprotective effects in different types of neurological diseases. However, its pharmacological function in traumatic brain injury (TBI) is still unknown. In the current study, a TBI model was constructed in mice to examine the potential beneficial roles of BEZ. After TBI, mice were daily dieted with BEZ or vehicle solution. The motor function, learning and memory, brain edema, vascular inflammatory factors, the integrity of the blood-brain barrier (BBB), and the expression of the tight junction zona occludens 1 (ZO-1) were assessed. The findings demonstrate that after TBI, BEZ treatment significantly promoted the recovery of motor function and cognitive function deficits. Moreover, BEZ attenuated brain edema by reducing the levels of brain water content. We also found that administration of BEZ alleviated cerebral vascular pro-inflammation by suppressing the expression of ICAM-1, VCAM-1, and <em>E</em>-selectin. Notably, BEZ improved the impaired BBB integrity in TBI mice by restoring the expression of the tight junction (TJ) protein ZO-1. Further in vitro experiments show that treatment with BEZ prevented the aggravation of endothelial permeability and restored the reduction of trans-epithelial electrical resistance (TEER) as well as the expression of ZO-1 in TBI-exposed brain bEnd.3 cells. Mechanistically, we prove that the protective effects of BEZ are mediated by AMPK. Based on these findings, we conclude that BEZ improves TBI-induced BBB injury and it might be considered for the treatment or management of TBI.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bee venom as a promising therapeutic strategy in central nervous system diseases","authors":"Zeinab Vahidinia ,&nbsp;Shirin Barati ,&nbsp;Abolfazl Azami Tameh ,&nbsp;Saeid Bagheri-Mohammadi ,&nbsp;Ali Garshasebi","doi":"10.1016/j.npep.2024.102451","DOIUrl":"10.1016/j.npep.2024.102451","url":null,"abstract":"<div><p>Central nervous system (CNS) disorders are one of the leading health problems today, accounting for a large proportion of global morbidity and mortality. Most these disorders are characterized by high levels of oxidative stress and intense inflammatory responses in degenerated neuronal tissues. While extensive research has been conducted on CNS diseases, but few breakthroughs have been made in treatment methods. To date, there are no disease-modifying drugs available for CNS treatment, underscoring the urgent need for finding effective medications. Bee venom (BV), which is produced by honeybee workers' stingers, has been a subject of interest and study across various cultures. Over the past few decades, extensive research has focused on BV and its therapeutic potentials. BV consists a variety of substances, mainly proteins and peptides like melittin and phospholipase A2 (PLA2). Research has proven that BV is effective in various medical conditions, including pain, arthritis and inflammation and CNS disorders such as Multiple sclerosis, Alzheimer's disease and Parkinson's disease. This review provides a comprehensive overview of the existing knowledge concerning the therapeutic effects of BV and its primary compounds on various CNS diseases. Additionally, we aim to shed light on the potential cellular and molecular mechanisms underlying these effects.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The activity of cholinergic neurons in the basal forebrain interferes with anesthesia-arousal process of propofol","authors":"Cai-hua Feng ,&nbsp;Xiao-Nan Du ,&nbsp;Zhi Wang ,&nbsp;Ting Wu ,&nbsp;Li-Na Zhang","doi":"10.1016/j.npep.2024.102449","DOIUrl":"10.1016/j.npep.2024.102449","url":null,"abstract":"<div><p>Previous research has demonstrated that basal forebrain (BF) regulates arousal during propofol anesthesia. However, as the BF comprises cholinergic neurons alongside two other types of neurons, the specific role of cholinergic neurons has not been definitively elucidated. In our study, calcium signal imaging was utilized to monitor the real-time activities of cholinergic neurons in the BF during propofol anesthesia. Additionally, we selectively stimulated these neurons to investigate EEG and behavioral responses during propofol anesthesia. Furthermore, we specifically lesioned cholinergic neurons in the BF to investigate the sensitivity to propofol and the induction time. The results revealed that propofol suppressed calcium signals of cholinergic neurons within the BF following intraperitoneal injection. Notably, upon recovery of the righting reflex, the calcium signals partially recovered. Spectral analysis of the EEG elucidated that optical stimulation of cholinergic neurons led to a decrease in δ power underlie propofol anesthesia. Conversely, depletion of cholinergic neurons in the BF enhanced sensitivity to propofol and shortened the induction time. These findings clarify the role of cholinergic neurons in the anesthesia-arousal process, as well as the depth and the sensitivity of propofol anesthesia.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417924000489/pdfft?md5=2954f2a19297b9c76679046ebce2f747&pid=1-s2.0-S0143417924000489-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141409489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MP-13, a novel chimeric peptide of morphiceptin and pepcan-9, produces potent antinociception with limited side effects","authors":"Chenxi Mei ,&nbsp;Jing Zhang ,&nbsp;Zhanyu Niu ,&nbsp;Jerine Peter Simon ,&nbsp;Tong Yang ,&nbsp;Mingmin Huang ,&nbsp;Zhonghua Zhang ,&nbsp;Lanxia Zhou ,&nbsp;Shouliang Dong","doi":"10.1016/j.npep.2024.102440","DOIUrl":"10.1016/j.npep.2024.102440","url":null,"abstract":"<div><p>Pharmacological investigations have substantiated the potential of bifunctional opioid/cannabinoid agonists in delivering potent analgesia while minimizing adverse reactions. Peptide modulators of cannabinoid receptors, known as pepcans, have been investigated before. In this study, we designed a series of chimeric peptides based on pepcans and morphiceptin (YPFP-NH₂). Here, we combined injections of pepcans and morphiceptin to investigate the combination treatment of opioids and cannabis and compared the analgesic effect with chimeric compounds. Subsequently, we employed computational docking to screen the compounds against opioid and cannabinoid receptors, along with an acute pain model, to identify the most promising peptide. Among these peptides, MP-13, a morphiceptin and pepcan-9 (PVNFKLLSH) construct, exhibited superior supraspinal analgesic efficacy in the tail-flick test, with an ED₅₀ value at 1.43 nmol/mouse, outperforming its parent peptides and other chimeric analogs. Additionally, MP-13 displayed potent analgesic activity mediated by mu-opioid receptor (MOR), delta-opioid receptor (DOR), and cannabinoid type 1 (CB1) receptor pathways. Furthermore, MP-13 did not induce psychological dependence and gastrointestinal motility inhibition at the effective analgesic doses, and it maintained non-tolerance-forming antinociception throughout a 7-day treatment regimen, with an unaltered count of microglial cells in the periaqueductal gray region, supporting this observation. Moreover, intracerebroventricular administration of MP-13 demonstrated dose-dependent antinociception in murine models of neuropathic, inflammatory, and visceral pain. Our findings provide promising insights for the development of opioid/cannabinoid peptide agonists, addressing a crucial gap in the field and holding significant potential for future research and development.</p></div><div><h3>Perspective</h3><p>This article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}