Molecular Biology Reports最新文献

{"title":"Pharmacological inhibition of the canonical Wnt/β-catenin signaling pathway sensitizes 5-fluorouracil-resistant colorectal cancer cells.","authors":"Diego Alfonso Arregui Ramos, Daniela Filomena Tavares de Pina, Annie Cristhine Moraes Sousa-Squiavinato, Wallace Martins de Araújo, Murilo Ramos Rocha, Jose Andres Morgado-Diaz","doi":"10.1007/s11033-026-12711-z","DOIUrl":"10.1007/s11033-026-12711-z","url":null,"abstract":"<p><strong>Background: </strong>The activation of the Wnt/β-catenin pathway with chemoresistance in colorectal cancer has been hypothesized. However, the use of specific inhibitors for targeting this pathway has not been well explored. In the present study, we analyze the activation of this pathway and its role in the stemness phenotype acquisition to regulate chemoresistance using our long-term 5-fluorouracil (5-FU) - resistant model of colorectal cancer cells, known to present epithelial-mesenchymal transition and enhanced migration and invasion.</p><p><strong>Methods and results: </strong>Initially by bioinformatic analyses we demonstrate the association between 5-FU resistance genes with those of a stem cell-like phenotype in patients with colon cancer. In addition, 5-FU-resistant cells displayed stemness characteristics, with upregulation of key stem cell marker (ALDH1A1) using reverse transcription-quantitative polymerase chain reaction. Further, 5-FU-resistant cells exhibited high Wnt/β-catenin pathway activity. Interestingly, treatment with LF3, an inhibitor of this pathway, re-sensitized the 5-FU-resistant cells, decreasing their proliferation.</p><p><strong>Conclusion: </strong>Wnt/β-catenin pathway activation plays a role in regulating key cellular events involved in chemoresistance. The study findings suggest the use of combinatorial therapies using conventional agents, such as 5-FU, and inhibitors of this pathway, as a useful therapeutic strategy to treat patients with colorectal cancer.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying low glycemic index in rice: Insights from Indian landrace diversity.","authors":"Jayasurya K, Utharasu S, Manonmani S, Umadevi M, Rajeswari R, Vanitha K","doi":"10.1007/s11033-026-12702-0","DOIUrl":"https://doi.org/10.1007/s11033-026-12702-0","url":null,"abstract":"<p><p>The rising prevalence of diabetes mellitus, especially among populations with high rice consumption, underscores the need for functional staple crops with a low glycemic index (GI). This review examines the molecular and genetic factors influencing low-GI traits in rice, highlighting the importance of diversity within Indian landraces. Traditional cultivars like Mappillai Samba, Karuppu Kavuni and Kattuyanam contains high level of Resistant starch, dietary fiber and bioactive phytochemicals. The Waxy (Wx) gene, which codes for granule-bound starch synthase I (GBSSI), is very important for controlling the production of amylose. For example, functional alleles like Wxa and Wxlv are linked to higher amylose levels and lower starch digestibility. Moreover, secondary metabolites, such as anthocyanins and phytosterols like stigmasterol, play a role in regulating blood sugar levels by stopping the activities of α-amylase and α-glucosidase. Interactions within the starch-dietary matrix, including starch-protein, starch-lipid, and starch-polyphenol complexes, further influence enzymatic hydrolysis and glucose release kinetics. Recent advancements in genomics, encompassing QTL mapping and gene editing techniques, offer innovative prospects for the creation of biofortified, low-GI rice cultivars. The integration of these molecular insights into rice breeding programs can facilitate the development of low-glycemic, nutritionally enhanced rice cultivars that contribute to improved metabolic health and food security.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome analysis of Brevibacterium sanguinis AZMABM HM27: a bacterial isolate from the sea anemone Radianthus magnifica and exhibiting promising multi-therapeutic properties.","authors":"Baso Manguntungi, Feraliana Feraliana, Azzahra Khasna Ramaniya, Joko Pebrianto Trinugroho, Wike Zahra Mustafawi, Herman Irawan, Agus Budiawan Naro Putra, Kartika Dyah Palupi, Santi Rukminita Anggraeni, M Fiqriansyah Wahab, Apon Zaenal Mustopa","doi":"10.1007/s11033-026-12717-7","DOIUrl":"https://doi.org/10.1007/s11033-026-12717-7","url":null,"abstract":"<p><strong>Background: </strong>The marine anemone Radianthus magnifica harbors symbiotic microbes with promising biomedical potential, yet their diversity and therapeutic properties remain underexplored. This study aimed to characterize a symbiotic bacterium isolated from R. magnifica collected from Samalona Island, Indonesia, and to evaluate its multi-therapeutic potential.</p><p><strong>Methods: </strong>Strain AZMABM HM27 was characterized using whole-genome sequencing, functional annotation, biosynthetic gene cluster prediction, molecular docking, and in vitro bioactivity assays.</p><p><strong>Results: </strong>Phylogenetic and genome-based analyses confirmed AZMABM HM27 as Brevibacterium sanguinis, with an OrthoANI value of 97.37% and a dDDH value of 76.50% against the type strain. The genome comprises a 3,834,082 bp chromosome encoding 3,362 protein-coding genes, including 95 genes involved in secondary metabolite biosynthesis. Five biosynthetic gene clusters were predicted, including those associated with ectoine, terpene, and siderophore production. The crude extract demonstrated antioxidant activity (IC₅₀ = 0.87 mg/mL), anti-inflammatory activity (up to 60% inhibition), antidiabetic activity through α-glucosidase inhibition (up to 40% inhibition), and dose-dependent antiproliferative activity against MCF-7 breast cancer cells (74.10% viability at 1 mg/mL). Molecular docking identified a lead compound, 8,9,9,10,10,11-hexafluoro-4,4-dimethyl-3,5-dioxatetracyclo [5.4.1.0(2,6)0.0(8,11)] dodecane, with strong binding affinities to selected therapeutic targets.</p><p><strong>Conclusions: </strong>B. sanguinis AZMABM HM27 represents a marine symbiotic strain associated with R. magnifica and a promising source of bioactive compounds with antioxidant, anti-inflammatory, antidiabetic, and antiproliferative potential. Further purification, structural elucidation, and in vivo studies are warranted to validate its therapeutic potential.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remodeling-phase wound-derived protein factors enhance mesenchymal stem cell function and improve diabetic wound healing.","authors":"Midhat B Zaidi, Shazmeen Aslam, Fatima Jameel, Irfan Khan, Asmat Salim","doi":"10.1007/s11033-026-12706-w","DOIUrl":"https://doi.org/10.1007/s11033-026-12706-w","url":null,"abstract":"<p><strong>Background: </strong>Chronic diabetic wounds result from dysregulated inflammatory responses and impaired progression from the inflammatory to proliferative and remodeling phases of healing. Although mesenchymal stem cells (MSCs) possess regenerative and paracrine potential, their function is compromised within the diabetic wound microenvironment. This study aimed to enhance wound healing by transplanting MSCs conditioned with remodeling-phase wound-derived factors.</p><p><strong>Methods: </strong>In this preclinical study, bone marrow-derived MSCs were isolated and characterized. Wound extracts from normal and streptozotocin-induced diabetic rats were evaluated, and the non-cytotoxic concentration (10 µg/mL) was used for conditioning. Functional assessment included in vitro scratch assays, gene expression analysis of inflammatory and regenerative mediators, and transplantation in a diabetic wound model, histological (H&E) and immunofluorescence (α-SMA) analyses.</p><p><strong>Results: </strong>Normal Day 9 wound extract (N9)-conditioned MSCs demonstrated enhanced wound closure in vitro. In contrast, Diabetic Day 9 wound extract (D9)-conditioned MSCs exhibited elevated expression of inflammatory genes and reduced expression of angiogenic and proliferative markers. In vivo, N9-conditioned MSCs significantly accelerated wound closure, restored tissue architecture, improved collagen organization, and increased the number of α-SMA-positive vascular structures, supporting enhanced vascular remodeling.</p><p><strong>Conclusion: </strong>Conditioning MSCs with remodeling-phase-derived factors present in normal Day 9 wound extract (N9) increases their therapeutic efficacy in diabetic wound healing. This preclinical strategy supports the use of phase-specific wound cues to optimize stem cell-based therapy and facilitate transition toward tissue regeneration.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desmoplakin loss in alveolar epithelium drives Wnt/β-Catenin-mediated extracellular matrix remodeling and fibrotic signaling in vitro.","authors":"Pooja Singh, Krishnendu Chakraborty, Aparna Bansal, Anurag Agrawal, Ritushree Kukreti","doi":"10.1007/s11033-026-12709-7","DOIUrl":"https://doi.org/10.1007/s11033-026-12709-7","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease characterized by aberrant extracellular matrix (ECM) remodeling, epithelial dysfunction, and limited therapeutic options. Genetic studies implicate Desmoplakin (DSP), a desmosomal adhesion protein, in IPF susceptibility; however, its mechanistic role remains unclear. This study aimed to investigate the role of DSP in regulating fibrotic and ECM remodeling pathways in alveolar epithelial cells.</p><p><strong>Methods and results: </strong>DSP was silenced using siRNA in adenocarcinoma-derived human alveolar epithelial A549 cells. DSP loss induced epithelial-to-mesenchymal transition, enhanced cell migration, and increased epithelial permeability, along with upregulation of fibrotic and ECM-associated genes. Pathway enrichment analysis of DSP interactors (STRING database) identified the Wnt/β-catenin signaling as a potential key pathway. Mechanistic validation using cycloheximide chase assays, qPCR, western blotting, immunofluorescence, and luciferase-reporter assays suggested that DSP loss destabilizes desmosomal complexes, promoting plakoglobin (γ-catenin) degradation while reducing β-catenin turnover. This was associated with increased nuclear accumulation of β-catenin and enhanced TCF/LEF-dependent transcription, leading to elevated expression of ECM-related genes, including COL1A1 and MMP9. DSP overexpression suppressed Wnt/β-catenin signaling and fibrotic gene expression, while pharmacological inhibition of this pathway attenuated DSP-dependent increases in ECM-associated gene expression.</p><p><strong>Conclusion: </strong>These findings suggest that DSP may function as a regulator of alveolar epithelial homeostasis and extracellular matrix remodeling in an in vitro epithelial model. Loss of DSP is associated with activation of Wnt/β-catenin-mediated fibrotic signaling, correlating with reduced plakoglobin stability. This study provides mechanistic insight into epithelial-matrix crosstalk in vitro and identifies a candidate pathway that may contribute to ECM dysregulation in IPF, the disease relevance of which will require validation in primary human alveolar epithelial cells and in vivo models.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oocyte quality in endometriosis-associated infertility: a narrative analysis of mechanisms and therapeutic options.","authors":"Lipsa Samal, Chidananda Dash, Sujata Pradhan","doi":"10.1007/s11033-026-12714-w","DOIUrl":"https://doi.org/10.1007/s11033-026-12714-w","url":null,"abstract":"<p><p>Endometriosis is a challenging gynaecological condition that can lead to infertility. This unique narrative review summarises the impact of endometriosis, focusing on oocyte quality, its subcellular and molecular mechanisms, clinical effects, and therapeutic options. The disease is associated with a hostile follicular microenvironment caused by inflammation, oxidative stress, granulosa and cumulus cell dysfunction, and hormonal dysregulation. It further leads to spindle disorders, mitochondrial DNA breakdown, and delayed cytoplasmic maturation. Women with stage III-IV endometriosis have low ovarian reserve, fewer retrieved and matured (MII) oocytes, and lower fertilisation and blastocyst development rates, resulting in worse cumulative pregnancy outcomes. However, when good-quality embryos are transferred, implantation and live birth rates are often similar to those of controls, suggesting that the problem is primarily oocyte-driven rather than endometrium-related. Therapeutic options include lifestyle modifications with a healthy diet, yoga, exercise, adequate sleep, and stress management, in addition to individualised assisted reproductive technology (ART) treatments, to enhance prognosis, though with sub-optimal proven mechanisms.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neem leaf glycoprotein mediated immunomodulation and epigenetic regulation in Acute Myeloid Leukemia.","authors":"Roshni Bibi, Shreyoshi Das, Subham Swopnil Deo, Srijita Sen, Sana Praveen, N M Pujitaa, R Pradeep, Melvin George, Koustav Sarkar","doi":"10.1007/s11033-026-12692-z","DOIUrl":"https://doi.org/10.1007/s11033-026-12692-z","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is associated with impaired antitumor immunity and defective activation of protective immune cells. Neem leaf glycoprotein (NLGP), an immunomodulatory component of neem leaf preparation, has demonstrated antitumor activity in several experimental models without apparent toxicity. This study investigated the immunomodulatory and epigenetic effects of NLGP on immune cells involved in tumor protection in AML.</p><p><strong>Methods: </strong>Peripheral immune cells from healthy individuals and AML patients were treated with NLGP. CD33 negative lymphocytes from AML patients were evaluated for lymphocyte proliferation, immune-cell activation, and secretion of the Th1-associated cytokines IFN-γ and TNF-α. Nitric oxide (NO₂⁻) release and reduced glutathione (GSH) content were also measured. The expression of Th1- and tumor-suppression-associated genes was analyzed. Chromatin immunoprecipitation was used to assess enrichment of active histone marks, including H3K4me3 and H3K14Ac, and repressive or regulatory markers, including H3K27me3, HDAC1, p53, Notch1, and c-Myc, at the IFNG and TBX21 loci. Cytotoxic T-lymphocyte (CTL)-mediated killing of AML cells was also examined.</p><p><strong>Results: </strong>NLGP enhanced lymphocyte proliferation and activated multiple immune-cell populations in normal subjects and AML-derived CD33 negative lymphocytes. It increased IFN-γ, TNF-α, and NO₂⁻ production while reducing GSH content. NLGP upregulated genes associated with Th1 immunity and tumor suppression. At the IFNG and TBX21 loci, it increased enrichment of H3K4me3, H3K14Ac, and p53, while reducing H3K27me3, HDAC1, Notch1, and c-Myc enrichment. NLGP also stimulated CTLs and enhanced their ability to eliminate AML cells.</p><p><strong>Conclusion: </strong>NLGP promotes tumor-protective immunity in AML through coordinated immune activation and epigenetic regulation, supporting its potential as a novel adjunctive immunotherapeutic strategy.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advancements in exosomal content analysis: the future of liquid biopsy.","authors":"Himadri Das Mohapatra, Samrat Banerjee, Lipsa Dash, Disha Ramnani, Pallavi Priyansi Jati, Preeti Basana Priyadarshini, Mrutyunjay Suar, Chinmaya Kumar Sarangi, Swastika Paul, Abhishek Dutta","doi":"10.1007/s11033-026-12661-6","DOIUrl":"https://doi.org/10.1007/s11033-026-12661-6","url":null,"abstract":"<p><p>Exosomes are widely acknowledged as an essential agent that carries biomarkers for specific diseases, representing the molecular status of their parent cells and providing extremely useful diagnostic insights. They can be isolated from different body fluids and contain a range of cargo molecules, including proteins, lipids, metabolites, and nucleic acids. Recent advancements in technology have greatly accelerated exosome research. Proteomics provides protein signatures linked to many pathological conditions, enabling quick and clinically scalable diagnostic tools, whereas high-throughput RNA-sequencing can be used to perform detailed transcriptome profiling. Exosomal biomarkers are showing promising clinical results in early detection of neurological diseases, infectious and cardiovascular disorders, oncology, and other medical conditions, hence accelerating therapeutic monitoring. Despite these advances, several challenges continue to hinder clinical translation including the lack of standardized isolation protocol, variability in exosome yield and purity, biological heterogeneity, and limited large-scale clinical validation. Addressing these limitations will be critical for the successful integration of exosome-based liquid biopsy into routine clinical practice. Overall, exosomes having significant potential as diagnostic tool, represent a transformative horizon in biomedical liquid biopsy research to redefine the landscape of less-invasive diagnostics and tailored clinical applications.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic and molecular effects of S-allylcysteine on uterine leiomyoma primary culture cells.","authors":"Sonia Narwal, Anumeha Vashist, Reetu Hooda, Kiran Siwach, Rohit Kaushik, Gulshan Rohilla, Nisha Khatri, Minakshi Vashist","doi":"10.1007/s11033-026-12708-8","DOIUrl":"https://doi.org/10.1007/s11033-026-12708-8","url":null,"abstract":"<p><strong>Background: </strong>Uterine leiomyomas (fibroids) are the third most common, hormone-dependent benign tumors characterized by abnormal cell proliferation and dysregulation of signalling pathways, particularly PI3K/AKT. S-Allylcysteine (SAC), a bioactive compound from aged garlic (Allium sativum), possesses anti-inflammatory and anticancer properties, but its effects on leiomyoma cells remain poorly understood.</p><p><strong>Aim: </strong>This study aimed to evaluate the cytotoxic effects of SAC on primary uterine leiomyoma culture cells and its molecular influence on PI3K/AKT pathway-related gene expression.</p><p><strong>Methods: </strong>A total of 25 uterine leiomyoma and 10 adjacent apparently normal myometrium paired tissues were collected from women with uterine leiomyoma. Of the 25 patients included for primary cell culture study, paired leiomyoma and adjacent myometrial tissues were obtained from 10 patients, while leiomyoma tissues alone were obtained from the remaining 15 patients. Primary uterine leiomyoma and adjacent myometrial cells were cultured in DMEM/F12 medium and treated with SAC (12.5-400 µg/ml) for 48 h. Cell viability was assessed by MTT assay, morphological changes were examined microscopically, and expression of PI3K (specifically PIK3R1), AKT3, MTOR, and PTEN was analysed by RT-qPCR using GAPDH as the housekeeping gene. Relative expression was calculated by the ΔΔCt method. Statistical analysis was performed using a one-way repeated-measures ANOVA test.</p><p><strong>Results: </strong>SAC significantly reduced ULPC viability in a dose-dependent manner, with an IC₅₀ of 255.71 ± 17.12 µg/ml (p < 0.05). Treated cells showed apoptotic features, including cell rounding, shrinkage, and reduced confluency. UMPC cells exhibited lower sensitivity, indicating a differential cytotoxicity response. SAC significantly downregulated transcript levels of PI3K, AKT3, and MTOR, while upregulating PTEN (p < 0.05).</p><p><strong>Conclusion: </strong>These findings indicate that SAC exerts selective cytotoxic effects on uterine leiomyoma cells, likely through modulation of the expression of selected PI3K/AKT pathway-related genes, supporting its potential as a therapeutic agent for uterine leiomyoma.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factors in Alzheimer's Disease pathogenesis: neuropharmacological implications for neuroprotection, neurogenesis, and therapeutic development.","authors":"Jahnvi Sehgal, Kajal Bagri, Rahul Deshmukh","doi":"10.1007/s11033-026-12698-7","DOIUrl":"https://doi.org/10.1007/s11033-026-12698-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by neuroinflammation, synaptic dysfunction, mitochondrial impairment, and cognitive loss. Despite extensive research, disease-modifying therapies remain elusive, underscoring the need to identify novel signalling pathways that could be pharmacologically modified. The diverse family of ligands known as fibroblast growth factors (FGFs) regulates neurogenesis, synaptic plasticity, neuronal survival, and metabolic balance by binding to fibroblast growth factor receptors (FGFRs). Numerous elements of AD pathogenesis, including energy metabolism, tau pathology, amyloid-β-toxicity, and neuroinflammation, are linked to dysregulated FGF-FGFR signalling according to an increasing number of studies. This study critically examines the neuropharmacological roles of FGFs in the central nervous system and their relationship to AD. We discuss how FGF modulates intracellular signalling cascades, including MAPK/ERK, PI3K-AKT, and STAT pathways, and how these changes affect synaptic integrity, glial activation, and neuronal resilience. We also highlight novel relationships among FGFs, metabolic dysfunction in AD, mitochondrial signalling, and gut-brain communication. Finally, we evaluate the therapeutic potential and challenges of targeting FGF signalling, including issues with receptor selectivity, blood-brain barrier penetration, and long-term safety. Collectively, this review positions FGF signalling as a promising yet underexplored neuropharmacological axis for developing disease-modifying strategies in Alzheimer's disease.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}