Neuropeptides最新文献

{"title":"PQK7: A novel peptide inhibitor targeting alpha-synuclein fibrillogenesis in Parkinson's disease","authors":"Maryam Motamedi ,&nbsp;Dina Morshedi ,&nbsp;Najaf Allahyari Fard","doi":"10.1016/j.npep.2025.102522","DOIUrl":"10.1016/j.npep.2025.102522","url":null,"abstract":"<div><div>The accumulation of alpha-synuclein (⍺-Syn) fibrils plays a central role in the progression of Parkinson's disease (PD) and related neurodegenerative disorders. In this context, the development of peptide inhibitors designed to inhibit ⍺-Syn through computational methods has emerged as a promising area of research. This study focused on developing a peptide inhibitor, PQK7, designed based on the key residues of NAC region of ⍺-Syn fibrils involved in its aggregation. Using molecular docking and dynamics simulations, PQK7 was shown to bind key residues in the NAC region of ⍺-Syn (Val-74, Ala-76, Val-77, Thr-81, Ser-87, Ile-88, and Ala-89), effectively disrupting the formation of fibrils. MD simulations indicated that the PQK7-⍺-Syn complex reaches a stable conformation, which showed increased fluctuations and reduced β-sheet content, suggests that PQK7 interferes with ⍺-Syn fibrillation at the molecular level. In vitro assays like ThT fluorescence assay, AFM imaging, CD specotroscopy, and SDS-PAGE analysis confirmed that PQK7 significantly reduces ⍺-Syn fibril formation, particularly at substoichiometric concentrations, while keeping ⍺-Syn monomers in a soluble state. Additionally, PQK7-⍺-Syn treatment in SH-SY5Y cells reduced the toxicity of ⍺-Syn aggregates, restoring normal cell cycle progression and reducing apoptosis and oxidative stress. Our findings suggest that PQK7 holds potential as a therapeutic agent for PD, acting as an anti-oligomeric inhibitor that targets early ⍺-Syn aggregates without affecting the protein's normal function.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102522"},"PeriodicalIF":2.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916682","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":"Interaction of glucocorticoids and interleukins in the control of hypothalamic neurohypophysial system output in salt loaded male rats","authors":"R.R. Ventura ,&nbsp;S.G. Ruginsk ,&nbsp;A. Lopes da Silva ,&nbsp;D. Badauê-Passos Jr ,&nbsp;H.D. Francescato ,&nbsp;T.M. Coimbra ,&nbsp;L.L.K. Elias ,&nbsp;J. Antunes-Rodrigues","doi":"10.1016/j.npep.2025.102523","DOIUrl":"10.1016/j.npep.2025.102523","url":null,"abstract":"<div><div>The present study investigated the effects of a 4-day salt load (0.3 M NaCl, SL) and dexamethasone treatment (DEXA, 1 mg/Kg, subcutaneous) on the mechanisms possibly underlying glucocorticoid-mediated effects on hypothalamic neurohypophyseal system (HNS) activity. As expected, SL animals developed hyperosmolality, reflecting the progressive increase in plasma sodium concentrations. SL also triggered increased hypothalamic expression of vasopressin (AVP) and oxytocin (OT) messenger RNAs (mRNAs), increased magnocellular neuronal activation, and enhanced plasma hormone concentrations. Plasma corticosterone, interleukin (IL) 1β and tumor necrosis factor alfa, but not IL-6 levels, were also elevated in response to SL. Increased salt consumption also significantly decreased hypothalamic mRNA expression for the p65 subunit of the nuclear factor kappa B (NFkB), and increased mRNA expression for type β NFkB inhibitory protein (IκBβ). The protein expression ratio between phosphorylated and total NFκB was also elevated in SL rats. DEXA administration, in turn, prevented SL-induced AVP and OT release, as well as decreased corticosterone/IL plasma levels. Therefore, the present results suggest that increased salt consumption may originate a systemic-driven pro-inflammatory response, which can contribute to the increased secretion of corticosterone observed in SL animals. We therefore hypothesize that elevated systemic IL levels, in parallel with corticosterone secretion, may constitute, besides hyperosmolality, important redundant stimuli triggering SL-induced neuropeptide release. Conversely, high levels of corticosterone would produce, in the long term, inhibition of HNS activity and the termination of the neurosecretory response.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102523"},"PeriodicalIF":2.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928148","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":"Netrin-3 enhances recovery and reduces inflammation following spinal cord injury via suppressing NLRP1 inflammasome activation","authors":"Zhe Li ,&nbsp;Xinghua Song ,&nbsp;Jialai Song","doi":"10.1016/j.npep.2025.102521","DOIUrl":"10.1016/j.npep.2025.102521","url":null,"abstract":"<div><div>Spinal cord injury (SCI) represents a significant challenge in the field of neurology due to its complex pathology and the limited efficacy of current treatments. The search for effective therapeutic strategies has led to investigations into molecules that can promote neural repair and functional recovery. Netrin-3, previously known for its roles in axonal guidance and development, emerges as a potential candidate for enhancing recovery post-SCI. Hereby, we used gene therapy to increase Netrin-3 expression in SCI mouse models and evaluated neurological recovery through behavioral tests, histological assessments, and biochemical analyses. Additionally, we examined the activation of the NOD-like receptor family pyrin domain containing 1 (NLRP1) inflammasome and production of interleukin-1β (IL-1β) and IL-18, and confirmed the dependency of Netrin-3's neuroprotective effects on the Adenosine Monophosphate-activated Protein Kinase (AMPK) pathway using an AMPK inhibitor. Our results explores the impact of Netrin-3 on neurological recovery following SCI. It was observed that Netrin-3 expression markedly decreased at both mRNA and protein levels after injury. Enhancing Netrin-3 levels through gene therapy improved neurological outcomes, including locomotor function, reduced lesion size, and normalized spinal cord water content compared to untreated injured mice. Furthermore, Netrin-3 administration mitigated oxidative stress by modulating malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, and inhibited NLRP1 inflammasome activation, resulting in suppressed IL-1β and IL-18 production. The AMPK pathway was activated by Netrin-3 post-injury, suggesting a mechanism underlying its neuroprotective effects. However, these beneficial impacts were abolished by an AMPK inhibitor, indicating the dependency of Netrin-3's protective actions on the AMPK pathway. Collectively, these findings highlight Netrin-3 as a promising target for developing novel therapies aimed at improving restoration from SCI.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102521"},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937226","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-like immunoreactivity in the skin and related sensory ganglia","authors":"Victoria Stöckl ,&nbsp;Georgios Blatsios ,&nbsp;Christian Humpel ,&nbsp;Zenon Pidsudko ,&nbsp;Vincenzo Provitera ,&nbsp;Germar-Michael Pinggera ,&nbsp;Teresa Rauchegger ,&nbsp;Josef Troger","doi":"10.1016/j.npep.2025.102520","DOIUrl":"10.1016/j.npep.2025.102520","url":null,"abstract":"<div><h3>Aim</h3><div>The chromogranin A-derived peptide catestatin has previously been shown to be a constituent of the sensory innervation of the eye and dental pulp. The antibody used in these studies not only recognizes authentic catestatin but also larger molecules containing the sequence of catestatin. Therefore, the authors now aimed to explore whether there are additional molecular forms present in the rat skin, rat trigeminal ganglion and rat dorsal root ganglia apart from free catestatin.</div></div><div><h3>Methods</h3><div>Western blot analysis was performed in these tissues and and double immunofluorescence techniques in rat dorsal root ganglia.</div></div><div><h3>Results</h3><div>A very prominent band was found at approximately 50 kDa in the skin representing a middle-sized fragment containing the sequence of this peptide. Recently, the same result has been obtained in the dental pulp indicating that this fragment might represent a main molecular form in various other tissues of the body. It is likely of sensory nature since the band was also present of weaker intensity both in the trigeminal ganglion and dorsal root ganglia and since abundant cells expressed catestatin-like immunoreactivity in rat dorsal root ganglia. Another small sized fragment of weaker intensity was found in these tissues as well. No band was observed in the position of intact chromogranin A in the Western blot.</div></div><div><h3>Conclusion</h3><div>Chromogranin A is proteolytically processed in sensory ganglia to at least two fragments containing the sequence of catestatin which are then anterogradely transported to the skin and the 50 kDa fragment obviously becomes aggregated there in nerve endings.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102520"},"PeriodicalIF":2.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760430","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":"Astrocyte Glucose-6-phosphorylase-Beta regulates ventromedial hypothalamic nucleus glucose counterregulatory neurotransmission and systemic hormone profiles","authors":"Karen P. Briski,&nbsp;Sushma Katakam,&nbsp;Subash Sapkota,&nbsp;Madhu Babu Pasula,&nbsp;Rami Shrestha,&nbsp;Rajesh Vadav","doi":"10.1016/j.npep.2025.102519","DOIUrl":"10.1016/j.npep.2025.102519","url":null,"abstract":"<div><div>Brain astrocytes generate free glucose at the conclusion of glycogenolysis or gluconeogenesis by glucose-6-phosphatase-beta (Glc-6-Pase-<em>β</em>) hydrolytic action. Astrocytes shape ventromedial hypothalamic nucleus (VMN) control of glucose counterregulation via lactate provision, yet possible effects of astrocyte endogenous glucose production are unknown. Current research investigated eu- and hypoglycemic patterns of VMN neuron counterregulatory neurotransmitter marker protein expression and counterregulatory hormone secretion following in vivo VMN astrocyte Glc-6-Pase-<em>β</em> gene-knockdown. Gene-silencing caused reductions in VMN astrocyte Glc-6-Pase-<em>β</em> protein expression and tissue glycogen and glucose content. Hypoglycemic suppression (dorsomedial VMN; VMNdm) or augmentation (ventrolateral VMN; VMNvl) of glycogen involves Glc-6-Pase-<em>β</em> –independent versus -dependent mechanisms, respectively. siRNA pretreatment reversed hypoglycemic down-regulation of VMNdm glucose levels and intensified up-regulated VMNvl glucose accumulation. Glc-6-Pase-<em>β</em> gene-knockdown correspondingly suppressed or enhanced baseline expression of glutamate decarboxylase_65/67 (GAD) and neuronal nitric oxide synthase (nNOS), protein markers for the counterregulation-inhibiting or -enhancing neurochemicals γ-aminobutyric acid and nitric oxide. Glc-6-Pase-<em>β</em> siRNA pretreatment did not alter hypoglycemic suppression of VMN GAD protein but reversed (VMNdm) or amplified (VMNvl) nNOS up-regulation. VMN Glc-6-Pase-<em>β</em> gene-silencing attenuated hypoglycemic patterns of corticosterone and growth hormone secretion and enhanced glucagon release. In summary, data provide unique evidence that VMN Glc-6-Pase-<em>β</em> activity affects glucose counterregulation. Outcomes document astrocyte Glc-6-Pase-<em>β</em> control of VMN glucose and glycogen accumulation as well as VMN neuron counterregulatory neurotransmission. Further research is warranted to identify Glc-6-Pase-<em>β</em> – mediated adjustments in astrocyte glucose metabolism that affect VMN GABAergic and/or nitrergic signaling within the brain glucostatic circuitry.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102519"},"PeriodicalIF":2.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679826","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":"Profile of cocaine and amphetamine regulated transcript peptide (CARTp) and Corticotropin-releasing factor (CRF) in the brain of Euphlyctis cyanophlyctis during puddle desiccation","authors":"Swapnil A. Shewale ,&nbsp;Sunil J. Koli ,&nbsp;Sneha Sagarkar ,&nbsp;Ameeta Ravikumar ,&nbsp;Shobha Bhargava","doi":"10.1016/j.npep.2025.102518","DOIUrl":"10.1016/j.npep.2025.102518","url":null,"abstract":"<div><div>During the post breeding season, anuran tadpoles are subjected to a wide range of environmental variables due to intermittent dry spells leading to pond desiccation. To avoid these harsh conditions, anurans accelerate rate of metamorphosis. In anurans, hypothalamic corticotropin-releasing factor (CRF) senses stress and activates metamorphosis via hypothamalo-pituitary- interenal/thyroid axis. Cocaine and amphetamine regulated transcript peptide (CARTp) is widely reported in the brains of vertebrates except reptiles. Role of CARTp along with CRF in mitigating the physiological effects of stress in mammals is well established. Therefore, we investigated effect of puddle desiccation on the CARTp and CRF peptide immunoreactivity in the brain of prometamorphic tadpoles of <em>Euphlyctis cyanophlyctis.</em> Animals in the naturally occurring desiccating puddle were fixed on field and the expression of CARTp and CRF were studied using immunohistochemistry. CARTp-immunoreactivity in entopeduncular nucleus (AEN and PEN), nucleus medialis septi (NMS) and hypothalamus (dHy and vHy) significantly increased in the prometamorphic tadpoles exposed to puddle desiccation as compared to controls. In preoptic area (POA) and Edinger Westphal nucleus (EW) significant increase in CARTp as well as CRF immunoreactive cells were observed in puddle desiccation group. Strong CRF immunoreactivity was observed in median eminence of stressed group. Puddle desiccation induced increase in the expression of CARTp and CRF peptide in the neuroendocrine axis may suggest their involvement in environmental stress induced accelerated metamorphosis. Moreover, elevated expression of CARTp but not CRF peptide in regions regulating energy homeostasis may indicate starvation due to scarcity of food or stress induced appetite suppression.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102518"},"PeriodicalIF":2.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670409","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":"Factors affecting the physical stability of peptide self-assembly in neurodegenerative disorders","authors":"Jahnu Saikia ,&nbsp;Mouli Sarkar ,&nbsp;Vibin Ramakrishnan","doi":"10.1016/j.npep.2025.102517","DOIUrl":"10.1016/j.npep.2025.102517","url":null,"abstract":"<div><div>Biological systems comprise of diverse biomolecules, including proteins, nucleic acids, lipids, and carbohydrates. Peptides, which are short chains of amino acids, exhibit unique properties when assembled to nano-level architectures. Self-assembling peptides possess a remarkable ability to organize into structured aggregates such as nanofibers, nanotubes, nanoribbons, and nanovesicles. These intricate structures are linked to neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Prion disease, Huntington's disease, and type II diabetes. Peptide nano assembly can be guided by external stimuli, such as temperature, pH, ultrasound, electric and magnetic fields. In this review, the discussion will be centred around the various factors that influence the self-assembly of peptides alongside therapeutic interventions that align with the fundamental principles of thermodynamics and kinetics to modulate the aggregation characteristics of peptide self-assembly.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102517"},"PeriodicalIF":2.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670407","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":"Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders","authors":"MD Nasiruddin Khan ,&nbsp;Divya Choudhary ,&nbsp;Sidharth Mehan ,&nbsp;Zuber Khan ,&nbsp;Ghanshyam Das Gupta ,&nbsp;Acharan S. Narula","doi":"10.1016/j.npep.2025.102516","DOIUrl":"10.1016/j.npep.2025.102516","url":null,"abstract":"<div><div>Neurological disorders, marked by progressive neuronal degeneration, impair essential cognitive functions like memory and motor coordination… This manuscript explores the significant roles of glial cell line-derived neurotrophic factor (GDNF), its co-receptors (GFRA1), and the receptor tyrosine kinase (RET) in mediating neuronal survival and function in various neurodegenerative conditions. The interplay between pivotal signaling pathways—PI3K/AKT and ERK1/2—facilitated by GDNF/GFRA1/RET, is emphasized for its neuroprotective effects. Dysregulation of these pathways is implicated in neurodegenerative and neuropsychiatric processes, with overactivation of GSK3β contributing to neuronal damage and apoptosis. Experimental evidence supports that activation of the RET receptor by GDNF enhances AKT signaling, promoting cell survival by inhibiting apoptotic pathways—therapeutic strategies incorporating GDNF delivery and RET activation present promising neuronal protection and regeneration options. Furthermore, inhibition of GSK3β demonstrates potential in ameliorating tau-related pathologies, while small molecule RET agonists may enhance therapeutic efficacy. This review explores the knowledge of GDNF/GFRA1/RET and PI3K/AKT/ERK1/2 associated signaling cascades, underscoring their significance in neuroprotection and therapeutic targeting to combat neurodegenerative diseases. Emerging approaches such as gene therapy and small-molecule RET agonists may offer novel avenues for treatment, although challenges like targeted delivery across the blood-brain barrier remain pertinent.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102516"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637309","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":"Bioactive peptides as multipotent molecules bespoke and designed for Alzheimer's disease","authors":"Ana Mesias,&nbsp;Sandra Borges,&nbsp;Manuela Pintado,&nbsp;Sara Baptista-Silva","doi":"10.1016/j.npep.2025.102515","DOIUrl":"10.1016/j.npep.2025.102515","url":null,"abstract":"<div><div>In an increasingly aging world where neurodegenerative diseases (NDs) are exponentially rising, research into more effective and innovative treatments seems paramount. Bioactive peptides (BPs) emerge as promising compounds with revolutionary potential in the treatment of NDs, particularly in well-known conditions like Alzheimer's disease (AD). The biological potential of these compounds is primarily attributed to their drug development advantages such as enhanced penetration, low toxicity, and rapid clearance, as well as, their antioxidant, and anti-inflammatory properties bio-linked to the neuroprotective effect, able to attenuate the multifactorial pathologies of AD. BPs can be sourced from common dietary origins, like animals, plants, marine, and from emerging sources like edible insects. However, to isolate an active BP with beneficial biological effects it must first be released from its parent protein, followed by a synthesis-flow. While <em>in silico</em> approaches can predict a BP's potential bioactivity and structural characteristics, <em>in vitro</em>, cell-based, and <em>in vivo</em> assays should be conducted to ensure these properties. The blood-brain-barrier (BBB) microenvironment and permeability in health or disease state are key factors to consider since they can limit the ability of circulating therapeutical agents, including BPs, to reach the brain. This review focuses on the bioactivity properties of BPs from different dietary protein sources and explores their beneficial effect and neuroprotective activity in AD, unraveling new paths of treatment.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102515"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563444","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":"Ginsenoside Rg1 improves autophagy dysfunction to ameliorate Alzheimer's disease via targeting FGR proto-oncogene","authors":"Qiankun Quan ,&nbsp;Xinxin Ma ,&nbsp;JianJun Feng ,&nbsp;Wanni Li ,&nbsp;Xi Li","doi":"10.1016/j.npep.2025.102514","DOIUrl":"10.1016/j.npep.2025.102514","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegeneration driven by beta-amyloid (Aβ) deposits in the brain involving autophagy dysfunction. Ginsenoside Rg1, a pharmacologically active compound found in ginseng, has possible therapeutic effects for AD. This study discovered that FGR proto-oncogene (FGR) was a therapeutic target of Rg1 in AD and it was possibly involved in autophagy. C57BL/6 J mice were injected with 5 μL (1 μg/mL) Aβ_1–42 in the right lateral ventricle to establish an AD model. AD mouse hippocampus had high FGR expression. Intragastrically administered Rg1 (40 mg/kg) decreased FGR protein levels in AD mice's hippocampus and improved memory function in AD mice. Both sides of the mice hippocampal fissure were administered with 2 μL lentiviral particles (1 × 10⁷ TU) containing FGR overexpression plasmids. FGR overexpression rendered Rg1 ineffectual in restoring memory function and reducing hippocampal neuron damage. We injected 2 μL lentiviral particles (1 × 10⁷ TU) containing short hairpin RNA plasmids targeting FGR to the mice hippocampal fissures. FGR knockdown improved spatial memory function of AD mice, reduced hippocampal neuron apoptosis, and prevented Aβ accumulation. HT22 cells were transfected with small interfering RNA targeting FGR. FGR knockdown increased the viability of Aβ_1–42 treated HT22 cells. BACE1 and LC3II/I protein levels were decreased and p62 and SIRT1 were increased in AD mice and cells with FGR knockdown. LC3 was down-regulated after inhibiting FGR expression in Aβ_1–42 treated hippocampal neurons. In conclusion, Rg1 exerts anti-AD functions by targeting FGR and downregulating its expression.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102514"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592338","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}