Biochemistry and Biophysics Reports最新文献

{"title":"Steroid hormone binding and modulation of Trichinella spiralis progesterone receptor: A computational approach","authors":"Muhammad Tahir Aleem ,&nbsp;Shakeel Ahmed Lakho ,&nbsp;Muhammad Mohsin ,&nbsp;Shahbaz Ul haq ,&nbsp;Ashiq Ali ,&nbsp;Danmei Huang ,&nbsp;Fenfei Gao","doi":"10.1016/j.bbrep.2025.102031","DOIUrl":"10.1016/j.bbrep.2025.102031","url":null,"abstract":"<div><div>Trichinellosis, caused by <em>Trichinella</em> species, including <em>Trichinella spiralis</em>, is a foodborne zoonotic disease. Upon ingestion, ML swiftly invade the intra-multicellular niche of the small intestine, undergoing four rapid molts to mature into adults. In general, the route of transmission for <em>T. spiralis</em> nematodes occurs through ingestion of pork. Therefore, it is crucial to develop a vaccine that can deal with trichinellosis, particularly for humans and pigs. In this study, homology modelling, molecular docking, simulations and molecular mechanics-based scoring (MM/GBSA) are used to investigate the interaction between <em>T. spiralis</em> membrane-associated progesterone receptor component 2 (<em>Ts</em>-MAPRC2) and different steroids hormones. In the most favorable region, 93 amino acid residues (92.1 %) are located, while 7 amino acids (6.9 %) are located in the allowed region, showing that the model with a 93.33 ERRAT quality factor is good quality. The MD simulations were conducted for 50 ns to explore the affinities and stability of four hormones chosen from the docking studies that showed similar binding poses to the control hormone Mifepristone. Simulations showed that the selected hormones were potent Ts-MAPRC2 binders and can act as leads to determine their activity by biophysical assays. Discovery of these five steroid hormones and interactions with Ts-MAPRC2 could lead to new therapies and vaccines for trichinellosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102031"},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8","authors":"Jianan Zhao ,&nbsp;Yunshen Li ,&nbsp;Runrun Zhang ,&nbsp;Yu Shan ,&nbsp;Chenyang Song ,&nbsp;Yaxin Cheng ,&nbsp;Yiming Shi ,&nbsp;Yixin Zheng ,&nbsp;Fuyu Zhao ,&nbsp;Junyu Fan ,&nbsp;Cen Chang ,&nbsp;Yuejuan Zheng ,&nbsp;Dongyi He","doi":"10.1016/j.bbrep.2025.102038","DOIUrl":"10.1016/j.bbrep.2025.102038","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates therapeutic gene targets and their epigenetic modifications in rheumatoid arthritis (RA), focusing on the molecular effects of methotrexate (MTX), Janus kinase (JAK) inhibitors, and (5R)-5-hydroxytriptolide (LLDT-8) on fibroblast-like synoviocytes (FLS).</div></div><div><h3>Methods</h3><div>Primary FLS were isolated from synovial tissues of RA and osteoarthritis (OA) patients and treated with MTX, JAK inhibitors, and LLDT-8. RNA sequencing identified differentially expressed genes (DEGs) under each treatment. The intersection of differentially expressed genes with trend analysis identified as potential drug target genes. Functional enrichment analyses were performed to explore associated pathways. Methylation changes in key genes were examined using the GEO database (GSE46364), and clinical relevance was evaluated using RA patient data from the PEAC database.</div></div><div><h3>Results</h3><div>Compared to the osteoarthritis FLS group, the RA FLS group showed significant differences in 5095 genes (3300 upregulated and 1795 downregulated). After JAK inhibitor treatment, 3795 significant differential genes were identified in RA FLS (1733 upregulated and 2062 downregulated). MTX treatment resulted in 3195 significant differential genes (2171 upregulated and 1023 downregulated), while LLDT-8 treatment revealed 12,993 significant differential genes (7801 upregulated and 5192 downregulated). Following trend analysis and de-duplication, we identified 45 important drug target genes that exhibited significant correlations with common clinical indices in RA patients. Among these, <em>GALNT9</em> and <em>CCNF</em> showed notable alterations in both methylation and expression levels, suggesting potential roles in RA pathogenesis and drug response. Functional enrichment highlighted critical pathways, including cell cycle, FoxO, and p53 signaling, which are implicated in FLS regulation and RA progression.</div></div><div><h3>Conclusion</h3><div>This study highlights therapeutic gene targets and their epigenetic modifications as potential mechanisms underlying the effects of MTX, JAK inhibitors, and LLDT-8 in RA treatment. <em>GALNT9</em> and <em>CCNF</em> emerge as promising candidates for further exploration in targeted therapeutic strategies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102038"},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine intestinal organoids cultured in an organ-on-a-chip microphysiological system","authors":"James Bacon,&nbsp;Halie Kitchel,&nbsp;John Stutz,&nbsp;Jack Hua Chen,&nbsp;Aaron Smith,&nbsp;Robert D. Van Horn,&nbsp;Christopher Moreland,&nbsp;Trent Abraham,&nbsp;Thomas Baker ,&nbsp;Eitaro Aihara,&nbsp;Kathleen Hillgren","doi":"10.1016/j.bbrep.2025.102036","DOIUrl":"10.1016/j.bbrep.2025.102036","url":null,"abstract":"<div><div>Preclinical studies are a vital component of pharmaceutical development and improvements in the predictive value of in vitro studies are essential. Organ-on-a-chip in vitro models are a recent advancement in the pursuit of improved reproduction of in vivo tissue complexity. Here, we report the development and characterization of porcine intestinal cells from organoids on chips with microfluid dynamics and peristaltic-like strain in a microphysiological system. Intestinal epithelial cells were grown on a porous membrane as a co-culture with human intestinal microvascular endothelial cells for up to 12 days. These cultures formed villi-like structures and established a tight barrier replete with F-actin and tight junctions. A demarcated region of the epithelial cells was in an actively proliferative stage, reminiscent of intestinal crypts. The intestinal epithelial cell growth was characterized for the presence of enterocytes, goblet cells and enteroendocrine cells. Notable drug transporters and CYP450 metabolic activity were present in these cultures. The organoid chip maintained barrier function as the paracellular permeability was low. In contrast, the permeability enhancer, sodium caprate (C₁₀), increased the apparent permeability of molecular weight marker compounds by 2- to 3-fold, and upon removal of C₁₀, the barrier was shown to be recovered. The porcine intestinal chip represents a new in vitro model with potential application in multiple aspects of pharmaceutical testing including drug metabolism, drug transporters and safety.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102036"},"PeriodicalIF":2.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting effects of acute versus chronic intermittent hypoxia on leptin secretion in differentiated human adipocytes – Implications for sleep apnea","authors":"Kiran R. Somers ,&nbsp;Christiane Becari ,&nbsp;Katarzyna Polonis ,&nbsp;Prachi Singh","doi":"10.1016/j.bbrep.2025.102030","DOIUrl":"10.1016/j.bbrep.2025.102030","url":null,"abstract":"<div><div>Obstructive sleep apnea (OSA) is a common sleep disorder associated with repetitive episodes of nocturnal intermittent hypoxia (IH), obesity and elevated leptin. Newly diagnosed OSA patients have a history of significant recent weight gain. While IH is implicated in OSA pathophysiology, the factors contributing to weight gain in OSA are not completely understood. Leptin is an adipokine with a central role in energy homeostasis and appetite control. Increases in leptin suppress appetite, while decreases in leptin increase appetite and may consequently cause weight gain. Using an <em>in vitro</em> approach, we examined the role of acute and chronic IH exposure on leptin secretion in differentiated human white preadipocytes. We show that acute 24-h exposure to IH and sustained hypoxia both increased leptin secretion, compared to normoxic controls (p = 0.01). In contrast, chronic repetitive IH exposure for 7 days decreased leptin secretion, compared to normoxic controls (p = 0.02). The decrease in leptin secretion during chronic IH exposure suggests a mechanism which may contribute to increased appetite and thereby predispose patients with untreated OSA to weight gain and obesity in early stages. As obesity progresses, leptin levels likely rise secondary to the increase in body fat. Elevated leptin levels in patients with longstanding OSA may be indicative of increased fat mass and not a consequence of IH-mediated effects on adipocytes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102030"},"PeriodicalIF":2.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes mellitus – conventional therapies and future perspectives in innovative treatment","authors":"Barbara Gieroba,&nbsp;Adrianna Kryska,&nbsp;Anna Sroka-Bartnicka","doi":"10.1016/j.bbrep.2025.102037","DOIUrl":"10.1016/j.bbrep.2025.102037","url":null,"abstract":"<div><div>Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and dysfunction of the pancreatic beta cells, which leads to elevated blood glucose levels. Conventional therapies, including metformin, sulfonylureas, and insulin, have long served as the cornerstone of treatment. However, they often face limitations, such as adverse effects, reduced efficacy over time, and difficulties in achieving optimal glycemic control. This has sparked considerable interest in developing novel and experimental therapeutic strategies to enhance treatment outcomes. Recent advances in diabetes management feature dual incretin receptor agonists, like tirzepatide, which combine GLP-1 and GIP receptor agonism, resulting in increased insulin secretion, decreased glucagon release, and significant weight loss. Additionally, dual SGLT1/2 inhibitors, such as sotagliflozin, show promise for more significant blood glucose reduction and improved weight loss by targeting glucose regulation in both the gut and kidneys. Other promising methods include glucagon receptor antagonists, GPR119 agonists, and FGF21 analogs, which strive to enhance insulin sensitivity and improve glucose metabolism through innovative pathways. Gene editing technologies, including CRISPR-Cas9 and AMPK activators, are also being investigated to tackle the underlying pathophysiology of T2DM more effectively. While these experimental therapies show promise, their long-term safety and efficacy remain under research. This article reviews the conventional therapies currently in use. It investigates future perspectives on innovative treatments for T2DM, emphasizing the potential of these new therapies to transform diabetes care and enhance patient outcomes.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102037"},"PeriodicalIF":2.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coenzyme Q10 and rikkunshito prevent age-related changes in mouse otolith morphology and function","authors":"Keita Ueda ,&nbsp;Takao Imai ,&nbsp;Tadao Okayasu ,&nbsp;Tatsuhide Tanaka ,&nbsp;Kouko Tatsumi ,&nbsp;Akio Wanaka ,&nbsp;Tadashi Kitahara","doi":"10.1016/j.bbrep.2025.102033","DOIUrl":"10.1016/j.bbrep.2025.102033","url":null,"abstract":"<div><div>Otoliths play an important role in maintaining body balance, and age-related decline in theis function and morphological integrity can lead to falls. In recent years, the herbal medicine rikkunshito (RKT) and the antioxidant coenzyme Q10 (CoQ10) have been studied for their anti-aging properties; however, their effects on otoliths remain unknown. Therefore, we aimed to investigate whether RKT and CoQ10 can prevent age-related functional and morphological changes in otoliths. To this end, 30 male and 30 female 8-week-old C57BL6N mice were used in this study. The mice were divided into three groups: a control group, CoQ10 group (0.2 % CoQ10 special diet), and RKT group (3 % RKT special diet). At 80 weeks of age, micro-computed tomography (μCT) images were taken and analyzed for otolith volume and CT number. Furthermore, eye movements induced by the linear vestibulo-ocular reflex (LVOR) were analyzed to assess otolith function.</div></div><div><h3>Results</h3><div>revealed that the RKT group had a significantly smaller volume of the 3 dimensional utriclar CT model (male mice; p = 0.0281, Steel test) and a significantly higher utricular CT number (male mice; p = 0.0104, Dunnett test) than the control group. The RKT group had a significantly weaker LVOR (male mice; lateral 1.3G stimulation; p = 0.00681, Dunnett test) (male mice; longitudinal 1.3G stimulation; p = 0.0183, Dunnett test) (male mice; longitudinal 0.7G stimulation; p = 0.00322, Dunnett test) than the control group. The CoQ10 group exhibited a significantly stronger utricle-induced LVOR than the control group (female mice; lateral 0.7G stimulation; p = 0.0133, Steel test).</div><div>In conclusion, RKT prevented age-related utricular morphological changes, but did not prevent age-related otolith functional changes in male mice. CoQ10 prevented age-related utricular functional changes for low frequency stimulation in female mice.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102033"},"PeriodicalIF":2.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA signaling in medicinal plants: An overlooked mechanism for phytochemical regulation","authors":"Esther Ugo Alum ,&nbsp;Chidozie Dennis Udechukwu ,&nbsp;David Chukwu Obasi","doi":"10.1016/j.bbrep.2025.102032","DOIUrl":"10.1016/j.bbrep.2025.102032","url":null,"abstract":"<div><h3>Background/objective</h3><div>Medicinal plants are invaluable sources of bioactive phytochemicals critical for global health. This mini review explores the role of RNA signaling in regulating phytochemical production in medicinal plants, highlighting its potential for optimizing their therapeutic potential.</div></div><div><h3>Methods</h3><div>This mini review integrates insights from recent studies published in Scopus and Web of Science (2019–2025) on RNA-mediated signaling, including small RNAs (sRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs).</div></div><div><h3>Results</h3><div>RNA signaling is revealed as a pivotal mechanism in secondary metabolite regulation, mediating stress-induced compound synthesis and environmental interactions. Notable findings include the role of siRNAs in activating alkaloid pathways and lncRNAs in regulating phenolic compound biosynthesis. RNA-directed DNA methylation and systemic RNA signaling further highlight its versatility in phytochemical regulation.</div></div><div><h3>Conclusion</h3><div>RNA signaling enhances medicinal plant research, unlocking therapeutic potential through bioactive compound production. The study calls for focused research to bridge knowledge gaps and translate laboratory findings into field applications.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102032"},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of early epileptic encephalopathy caused by new mutation at W218C in KCNQ2 and review literature","authors":"Juhua Yang ,&nbsp;Yuping Huang ,&nbsp;Zhijun Chen ,&nbsp;Jiaheng Peng ,&nbsp;Kangyu Li ,&nbsp;Lijuan Huang ,&nbsp;Jie Yang ,&nbsp;Chunhui Yang","doi":"10.1016/j.bbrep.2025.102008","DOIUrl":"10.1016/j.bbrep.2025.102008","url":null,"abstract":"<div><div>Early-onset epileptic encephalopathy (EOEE) is mainly characterized by early refractory epileptic seizures in infants with progressive brain dysfunction, accompanied by complex causes (such as perinatal brain injury, structural brain malformations and genetic metabolic diseases). Early identification and etiological treatment are critical. It has been reported that mutations in Potassium Voltage-Gated Channel Subfamily Q Member 2 (<em>KCNQ2</em>) can result in EOEE. This study analyzed the genetic defects and clinical phenotypes of a newborn with early epileptic encephalopathy. Whole exome gene detection identified a novel heterozygous point mutation p. W218C in <em>KCNQ2.</em> The pathogenic variant was located in the protein's S4S5 connection region and was identified as a harmful mutation by silico tools. The child's clinical phenotype finally manifested as West syndrome during the follow-up. The mentioned variation may lead to severe clinical manifestations and poor neurological prognosis. Whole exome gene detection provides clinicians with more information on neonatal epileptic encephalopathy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102008"},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC16A3 (MCT4) expression in tumor immunity and Metabolism: Insights from pan-cancer analysis","authors":"Wenxing Du ,&nbsp;Bo Zang ,&nbsp;Yang Wo ,&nbsp;Shiwei Chen","doi":"10.1016/j.bbrep.2025.102034","DOIUrl":"10.1016/j.bbrep.2025.102034","url":null,"abstract":"<div><h3>Background</h3><div>SLC16A3, a highly expressed H + -coupled symporter, facilitates lactate transport via monocarboxylate transporters (MCTs), contributing to acidosis. Although SLC16A3 has been implicated in tumor development, its role in tumor immunity remains unclear.</div></div><div><h3>Methods</h3><div>A pan-cancer analysis was conducted using datasets from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, and Genotype-Tissue Expression projects. SLC16A3 expression patterns and associations with tumor progression, prognosis, immune checkpoints, and immune neoantigens were evaluated across 30 cancer types. Immune infiltration scores were analyzed using the Tumor Immune Estimation Resource dataset.</div></div><div><h3>Results</h3><div>SLC16A3 expression is differentially regulated in cancer versus healthy tissues, with elevated levels associated with poor prognosis and reduced overall survival in glioblastoma multiforme (HR = 1.88), low-grade gliomas (HR = 1.51), and lung adenocarcinoma (HR = 1.33). Notably, significant associations between SLC16A3 expression and poor outcomes were observed in 33 cancers, except for rectum adenocarcinoma, testicular germ cell tumors, pheochromocytoma and paraganglioma, and adrenocortical carcinoma. SLC16A3 expression was also strongly linked to immune checkpoints and neoantigens. Correlations with tumor-infiltrating immune cells were pronounced in prostate adenocarcinoma but absent in uterine carcinosarcoma and cervical squamous cell carcinoma. Gene set enrichment analysis (GSEA) revealed a pivotal role of SLC16A3 in tumor growth, metabolism, and immunity.</div></div><div><h3>Conclusion</h3><div>SLC16A3, the transporter facilitating the efflux of lactic acid, shows differential expression across various cancer types and exerts a critical effect on tumor development and immunity. Thus, SLC16A3 has promising potential as a prognostic marker, and its targeted manipulation can offer therapeutic advantages.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102034"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease","authors":"Huijun Li ,&nbsp;Yawei Fan ,&nbsp;Chan Chen ,&nbsp;Yuzhong Xu ,&nbsp;Xiong Wang ,&nbsp;Wei Liu","doi":"10.1016/j.bbrep.2025.102035","DOIUrl":"10.1016/j.bbrep.2025.102035","url":null,"abstract":"<div><h3>Background</h3><div>Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weighted gene co-expression network analysis (WGCNA), and synaptic-related genes. The overlapped hub genes were further processed using machine learning algorithms, intersected with module gene from protein-protein interaction (PPI) network constructed with DEGs, to yield co-hub genes. The diagnostic potentials of the co-hub genes were examined by receiver operating characteristic (ROC) analysis. Correlation between co-hub genes with clinical features and immune cell infiltration was analyzed. Finally, the expression of co-hub genes was analyzed in several datasets and validated in AD transgenic mice.</div></div><div><h3>Results</h3><div>A total of three co-hub genes were identified, including MAP1B, L1CAM, and GABBR2. GABBR2 showed area under the curve (AUC) values of 0.98, 0.81, and 0.88 in the training and two external validation datasets. GABBR2 was negatively correlate with beta- and gamma-secretase activities, and infiltration of natural killer T cells and effector memory CD8 T cells. Finally, GABBR2 was validated to be downregulated in AD transgenic mice, aligning with bioinformatic findings. GABBR2 overexpression in N2a/APP cells increased ADAM10 while decreased of BACE1, leading to upregulation of sAPPα while downregulation of sAPPβ.</div></div><div><h3>Conclusion</h3><div>In conclusion, GABBR2 acts as a novel biomarker for the diagnosis of AD and negatively correlated with Aβ in AD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102035"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}