Neuropeptides最新文献

{"title":"Salivary oxytocin responses in mothers and full-term newborns in early skin-to-skin contact for the first 2 hours after birth: Effects of synthetic oxytocin administration and epidural analgesia in labor","authors":"Aya Tomita,&nbsp;Kaori Yonezawa,&nbsp;Yuriko Usui,&nbsp;Megumi Haruna","doi":"10.1016/j.npep.2025.102567","DOIUrl":"10.1016/j.npep.2025.102567","url":null,"abstract":"<div><h3>Background</h3><div>Epidural analgesia with synthetic oxytocin reduces maternal oxytocin levels in the early postpartum period. However, whether maternal and neonatal endogenous oxytocin levels in the first 2 h after birth are affected by drug administration during labor is unknown.</div></div><div><h3>Aim</h3><div>To determine the effect of drug administration during labor on maternal–newborn salivary oxytocin levels after birth.</div></div><div><h3>Methods</h3><div>This cohort study was conducted on 62 stable primiparous mother–newborn pairs after vaginal birth. Saliva samples were collected approximately 30 (pre-skin-to-skin contact), 60 (during skin-to-skin contact), and 120 (post-skin-to-skin contact) minutes after birth. Mother–newborn pairs were stratified by medical interventions during labor: non-drug, oxytocin-only, and epidural analgesia-with-oxytocin groups. A mixed-effects model was used to evaluate the log-transformed salivary oxytocin levels among the three groups at each repeated measure.</div></div><div><h3>Results</h3><div>Maternal oxytocin levels of the epidural analgesia-with-oxytocin group (β = − 0.384, standard error = 0.113) were significantly lower than those of the non-drug group at 30 min (<em>p</em> &lt; 0.001). The group-time interaction analysis showed that the changes in salivary oxytocin levels in the oxytocin-only and epidural analgesia-with-oxytocin groups differed from those in the non-drug group at 60 and 120 min. Newborn oxytocin levels did not significantly differ.</div></div><div><h3>Conclusions</h3><div>Drug administration during labor may reduce maternal salivary oxytocin levels in the first 2 h after birth. Healthcare professionals should provide information on different approaches, such as a non-pharmacologic approach, for pain relief for primipara during labor.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102567"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459409","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":"Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases","authors":"Sushil Giri,&nbsp;Phool Chandra","doi":"10.1016/j.npep.2025.102563","DOIUrl":"10.1016/j.npep.2025.102563","url":null,"abstract":"<div><div>Neurodegenerative disorders (NDDs) pose a growing global health burden, primarily due to their progressive nature and the limited efficacy of existing treatments. Bioactive peptides and proteins/polypeptides, particularly those derived from dietary and natural sources, show promise in modulating neurobiological pathways central to neurodegeneration. This review aims to critically examine the neuroprotective roles of Bioactive peptides and proteins/polypeptides in NDDs, elucidating their mechanisms of action, potential therapeutic applications in conditions like Alzheimer's, Parkinso's disease, Huntington's disease, and others, as well as the trends in peptide-based therapeutics. Bioactive peptides and proteins/polyspeptides, such as NGF, BDNF, GDNF, Semax, and Exendin-4, have been found to modulate several critical mechanisms, including the reduction of oxidative stress (OS), inhibition of neuroinflammation, preservation of mitochondria, and enhancement of synaptic plasticity. These peptides have demonstrated efficacy in preclinical and early-phase clinical trials across a spectrum of NDDs. Delivery challenges, such as blood-brain barrier (BBB) permeability and enzymatic degradation, have been acknowledged. Ongoing innovations in peptide engineering, nanoparticle-based delivery systems, CRISPR-assisted design, and AI-driven screening are addressing these limitations. By targeting multiple pathogenic mechanisms simultaneously, peptide-based therapeutics present a rational and innovative approach to NDD management. Their multifunctional action profiles and ability to target specific molecular pathways highlight their potential as next-generation neuroprotective agents. However, future clinical validation and advanced strategies are essential for translating these promising molecules into effective treatments.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102563"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155841","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":"Kisspeptin-54 ameliorates chondrocyte senescence in osteoarthritis via SIRT3-mediated telomere protection and p53 acetylation inhibition","authors":"Zhuobin Yang,&nbsp;Jimo Li,&nbsp;Wenfeng Jin,&nbsp;Dongfeng Cai,&nbsp;Jing Zhang,&nbsp;Song Hong","doi":"10.1016/j.npep.2025.102562","DOIUrl":"10.1016/j.npep.2025.102562","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA), characterized by chondrocyte senescence and oxidative stress, affects over 300 million people globally. Kisspeptin-54, a neuropeptide with pleiotropic protective effects, was investigated for its role in chondrocyte senescence and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Oxidative stress and senescence were induced in primary mouse chondrocytes by treating them with TBHP. Kisspeptin-54 was administered at varying concentrations (10–1000 nM) to assess cytoprotection, while SIRT3 was knocked down using adenoviral shRNA to validate mechanistic pathways. Telomere length, mTERT expression, telomerase activity, and p53 acetylation were evaluated via Southern blot, RT-PCR, and western blot techniques. Furthermore, senescence was evaluated through the application of SA-β-galactosidase staining alongside the measurement of PAI-1 expression.</div></div><div><h3>Results</h3><div>TBHP induced dose-dependent GPR54 downregulation, oxidative stress (260 % increase in ROS), telomere attrition (41 % reduction in length), and senescence (270 % increase in SA-β-galactosidase-positive cells). Kisspeptin-54 (≤200 nM) rescued cell viability, reduced LDH release (57 % at 200 nM), and mitigated ROS and SOD activity decline. Mechanistically, Kisspeptin-54 restored SIRT3 expression, suppressed p53 acetylation (Acetyl-p53[K382] reduced by 56 % at 200 nM), and preserved telomere function (telomere length restored to 91 % of control). SIRT3 knockdown abrogated these effects, confirming its critical role.</div></div><div><h3>Conclusion</h3><div>Kisspeptin-54 alleviates chondrocyte senescence via a dual mechanism: (1) SIRT3-mediated restoration of mitochondrial antioxidant capacity and telomere homeostasis; (2) inhibition of p53 hyperacetylation and downstream senescence signaling. These findings establish Kisspeptin-54 as an innovative therapeutic candidate for OA acting through the modulation of the SIRT3/p53 axis to combat oxidative stress and telomere dysfunction.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102562"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192092","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":"Chromogranin B: A versatile neuroendocrine protein regulating physiological and metabolic functions","authors":"Chandramouli Mukherjee,&nbsp;Palki Chauksey,&nbsp;Aamna Jain,&nbsp;Bhavani S. Sahu","doi":"10.1016/j.npep.2025.102548","DOIUrl":"10.1016/j.npep.2025.102548","url":null,"abstract":"<div><div>Chromogranin B (CHGB) is a key member of the granin family of acidic proteins, predominantly localized in the secretory granules of professional secretory cells, such as neurons and neuroendocrine cells. It plays a crucial role in the regulated secretory pathway, influencing hormone storage, processing, and release. CHGB's role extends from cellular processes to systemic physiology, encompassing vesicular trafficking, calcium homeostasis, and immune regulation. CHGB dysfunction is linked to pathological conditions such as neurodegenerative diseases, cardiovascular disorders, and metabolic disorders. This review examines the multifaceted functions of CHGB at both the cellular and organismal levels, highlighting its role in maintaining cellular homeostasis and its potential link to metabolic dysfunction and related pathophysiology.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102548"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826687","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":"Interplay of neuropeptide Y and autophagy in Alzheimer's disease: Therapeutic perspectives and mechanistic insights","authors":"Dhiraj Lanjewar,&nbsp;Raj Katariya,&nbsp;Vinita Kale,&nbsp;Brijesh Taksande,&nbsp;Milind Umekar,&nbsp;Madhura Vinchurney","doi":"10.1016/j.npep.2025.102547","DOIUrl":"10.1016/j.npep.2025.102547","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive, chronic, neurodegenerative disorder involving cognitive impairment, neuronal loss, autophagy dysregulation, and toxic protein aggregates build-up, including amyloid-β plaques and hyperphosphorylated tau tangles. Autophagy dysregulation is a central driving force behind AD pathogenesis, interfering with the clearance of these aggregates and resulting in synaptic disruption and enhanced neurodegeneration. Neuropeptide Y (NPY) is abundantly present in the CNS. NPY has been identified as a promising candidate due to its neuropeptidergic activity. It plays a central role in regulating autophagy, anti-inflammation, and the induction of synaptic plasticity. NPY regulates the AMPA-mTOR pathway to restore cellular homeostasis and enhance neuronal survival through improved autophagic flux. It facilitates the clearance of aggregate proteins and dysfunctional cellular components, which lessen the signs of AD pathology. Moreover, NPY plays an important role in stabilizing the mitochondria and enhancing antioxidant action, in effect sustaining cognitive function. The modulatory influence of NPY on autophagy represents a potential novel direction in AD therapy, advanced delivery systems, such as nanoparticle-based carriers, offer promising targeted brain delivery mechanisms. However, clinical application is hindered by the need for a receptor-specific agonist to mitigate side effects and the lengthy trials necessary to assess long-term efficiency. Further research should aim to optimise NPY delivery and autophagy-targeted therapies to develop more effective treatments; such research challenges may position NPY as a breakthrough candidate for slowing cognitive and functional impairment in AD.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102547"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679854","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":"Irisin alleviates anxiety and deficits in fear extinction in PTSD within SPS mouse model","authors":"Xupei Xie ,&nbsp;Yandi Ding ,&nbsp;Qizhi Yan ,&nbsp;Jiadan Zhao ,&nbsp;Lingdi Zhang","doi":"10.1016/j.npep.2025.102537","DOIUrl":"10.1016/j.npep.2025.102537","url":null,"abstract":"<div><div>Post-Traumatic Stress Disorder (PTSD), a prevalent psychological disorder, emerges subsequent to a grave traumatic incident or a succession of such events. Irisin is expressed in brain regions such as the hippocampus and prefrontal cortex and is found to have a neuroprotective function by suppressing neuroinflammation through the AMPK pathway, demonstrating its potential in treating cognitive decline, having antidepressant effects, and intervening in stress-related disorders. This study aims to explore the potential therapeutic effects of irisin on PTSD, as well as investigate the underlying mechanisms. Results showed that SPS caused anxiety-like behaviors and deficit in fear memory extinction of the mice. These SPS-induced abnormalities of the mice were reversed by exogenous irisin treatment. However, the AMPK inhibitor abolished the protective effects of irisin, indicating that irisin's therapeutic effects on SPS mice were achieved by activating AMPK. Further biochemical experiments demonstrated that irisin could increase pAMPK levels and ameliorate the overexpression of NF-κB and its downstream factors, including inflammatory factors and neurotoxic mediators, in the hippocampus, frontal cortex, and amygdala of the SPS mice. These effects of irisin were also reversed by AMPK inhibitor. Cell experiments suggest that irisin exerts anti-inflammatory effects on BV2 cells (microglia) via the AMPK/NF-κB pathway and subsequently confers anti-inflammatory benefits while enhancing cell viability in PC12 cells. The cumulative results indicate that irisin can improve behavioral deficits induced by SPS in mice by exerting anti-neuroinflammation function, and this function may be associated with the modulation of AMPK/NF-κB pathway in microglia in the brain tissues including hippocampus, cerebral cortex, and amygdala.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102537"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653283","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":"Substance P mitigates lipopolysaccharide induced cognitive impairment in rats in a dose dependent manner","authors":"Prasada Chowdari Gurram ,&nbsp;Suman Manandhar ,&nbsp;Sairaj Satarker ,&nbsp;Ajmal Nassar ,&nbsp;Farmiza Begum ,&nbsp;Jayesh Mudgal ,&nbsp;Devinder Arora ,&nbsp;Madhavan Nampoothiri","doi":"10.1016/j.npep.2025.102551","DOIUrl":"10.1016/j.npep.2025.102551","url":null,"abstract":"<div><div>Neuroinflammation contributes to cognitive decline in Alzheimer's disease (AD), and the neurokinin pathway has been implicated in the pathophysiology of AD. Although Substance P (SP), an endogenous ligand to the neurokinin 1 receptor (NK1R), is primarily known as a neurotransmitter, but emerging evidence indicates it has shown both pro and anti-inflammatory actions. However, the dose-dependent nature of the SP–NK1R axis’s functional role remains to be fully elucidated. In this study, we examined the effects of SP in a rat model of AD induced by lipopolysaccharide (LPS).</div><div>A dose of 150 μg/10 μl of LPS was administered through intracerebroventricular injection to induce cognitive impairment in the rats. Two doses of SP, 50 μg/kg and 500 μg/kg were administered intraperitoneally once a day for 21 days. Behavioral assessments included the Morris water maze test and novel object recognition test to investigate cognitive defects, and the open field test evaluated locomotion. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), amyloid-beta (Aβ), acetylcholinesterase (AChE), lipid peroxidation, and catalase were estimated in the frontal cortex and hippocampus. The cAMP-responsive element-binding (CREB) protein levels in the whole brain were estimated by western blot. The LPS treatment significantly impaired cognition, increased levels of cytokines, Aβ, oxidative stress, and AChE, while decreasing CREB levels. Notably, the lower dose of SP (50 μg/kg) restored cognitive performance and markers of AD. In contrast, the higher dose of SP (500 μg/kg) failed to reverse spatial memory impairment and neuroinflammation. Thus, our data propose the dose-dependent effect of SP on neuroinflammation-induced cognitive deficits in AD.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102551"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903012","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":"Inhibition of neurokinin B promotes functional recovery in traumatic brain injury by increasing M2 microglia","authors":"Fangjie Luo ,&nbsp;Xiaoyun Li ,&nbsp;Zhanpeng Zhu","doi":"10.1016/j.npep.2025.102549","DOIUrl":"10.1016/j.npep.2025.102549","url":null,"abstract":"<div><div>Microglial polarization into pro-inflammatory M1 and anti-inflammatory M2 phenotypes is critical for regulating neuroinflammation and tissue repair following traumatic brain injury (TBI). The M1/M2 balance determines neurological outcomes, yet the mechanisms governing this polarization remain unclear. This study identifies neurokinin B (NKB) as a novel regulator of microglial M1/M2 polarization in TBI. Using a murine TBI model, we demonstrated significant upregulation of NKB and its receptor NK3R. Genetic knockdown of NKB enhanced functional recovery and shifted microglial polarization from the detrimental M1 to the beneficial M2 phenotype. Conversely, NKB administration promoted M1 activation while suppressing M2 markers in microglial cultures, potentially through inhibition of the STAT6 pathway. Overexpression of STAT6 reversed NKB's suppressive effects on M2 polarization, while NK3R antagonism with SB222200 promoted M2 polarization and improved functional outcomes. These findings establish NKB signaling as a key modulator of microglial dynamics after TBI, suggesting that targeting this pathway may promote neuroprotective M2 polarization while inhibiting damaging M1 responses. This dual regulation, combined with improved cognitive recovery, positions NKB as a promising target for developing novel TBI therapies aimed at modulating neuroinflammation.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102549"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829599","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":"Catestatin attenuates cerebral ischemia/reperfusion injury and suppresses endoplasmic reticulum stress","authors":"Xiaodong Zhang,&nbsp;Jiaxin Fan,&nbsp;Shuyin Ma,&nbsp;Nan Zhang,&nbsp;Kaili Shi,&nbsp;Mengying Chen,&nbsp;Minyu Duan,&nbsp;Qingling Yao,&nbsp;Yuxuan Cheng,&nbsp;Shuang Du,&nbsp;Huiyang Qu,&nbsp;Han Yang,&nbsp;Tiantian Gao,&nbsp;Shuqin Zhan","doi":"10.1016/j.npep.2025.102550","DOIUrl":"10.1016/j.npep.2025.102550","url":null,"abstract":"<div><div>Ischemic stroke is one of the leading causes of death worldwide. Catestatin (CST), as a pleiotropic hormone, displays an anti-apoptotic effect, in addition to its known roles in cardiovascular regulation. However, the role of CST in ischemic stroke remains unclear. In this study, we investigated the temporal changes of CST levels in the cortex and serum of middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Intracerebroventricular administration of CST significantly alleviated neurological deficits, reduced cerebral infarct volume, cerebral edema, and pathological damage, while attenuating neuronal apoptosis and modulating apoptosis-related proteins. Notably, CST suppressed endoplasmic reticulum stress (ERS) by inhibiting the PERK pathway. Furthermore, in vitro experiments using the oxygen-glucose deprivation/reperfusion (OGD/R) model of PC12 cells demonstrated that CST similarly inhibited apoptosis, as evidenced by flow cytometry and consistent changes in apoptosis-related proteins. These findings collectively demonstrate that CST exerts neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI), with these effects potentially mediated through inhibition of ERS via the PERK signaling pathway.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"113 ","pages":"Article 102550"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829600","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":"Neuroprotective effect of Ac-SDKP peptide in SH-SY5Y cells and rat model of Parkinson's disease against 6-OHDA-induced oxidative stress and ER stress","authors":"Maryam Kamarehei ,&nbsp;Hamid Zahednasab","doi":"10.1016/j.npep.2025.102534","DOIUrl":"10.1016/j.npep.2025.102534","url":null,"abstract":"<div><div>Oxidative stress and endoplasmic reticulum (ER) stress are key contributors to the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD), for which no definitive cure currently exists. This study investigated the neuroprotective potential of the <em>N</em>-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) tetrapeptide in both in vitro and in vivo PD models. In cell-based analyses, pre-treatment with 20 nM Ac-SDKP provided significant protection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells. In vivo, the neuroprotective potential of the peptide was also supported through daily administration of rats with Ac-SDKP (800 μg/kg) after 6-OHDA lesioning, which unveiled a series of significant observations. Treated animals demonstrated highly preserved dopaminergic neurons through reduced activation of apoptotic markers such as caspase-3 and caspase-12. In addition to cytoprotection, Ac-SDKP also produced striking behavioral improvement. Treated animals exhibited improved motor coordination and ability on spatial memory tasks, as well as the significant attenuation of anxiety-like and depressive-like behaviors. Such behavioral improvement is probable because Ac-SDKP possesses the ability to modulate several pathological features of PD. In fact, the peptide was able to decrease oxidative stress, diminish ER stress, and inhibit neuroinflammatory signaling. Collectively, these findings position Ac-SDKP as a promising neuroprotection candidate, and as a candidate with potential to be developed as a multifactorial treatment for the complex pathophysiology of PD.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"112 ","pages":"Article 102534"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330967","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}