Chemical biology & drug design最新文献

{"title":"Emerging Design Principles at the Forefront of Mitochondrial Transplantation Using Engineering Methodologies: Current Achievements and Future Directions.","authors":"Naoto Yoshinaga, Keiji Numata","doi":"10.1111/cbdd.70296","DOIUrl":"10.1111/cbdd.70296","url":null,"abstract":"<p><p>Mitochondrial transplantation has gathered much attention as therapeutics to improve multiple mitochondrial functions simultaneously. While the administration of naked mitochondria into the target tissue has demonstrated therapeutic outcomes sufficient to advance to clinical trials, there remain many limitations, including a low cellular uptake efficiency in the target tissue and dysfunction of the isolated mitochondria. To address these issues, engineering approaches have been developed to functionalize the isolated mitochondria. In this review, we focus on the three critical topics for efficient mitochondrial transplantation and outline emerging design rules and their limitations for each purpose: (i) tissue targeting, (ii) protection of mitochondria from external stresses, and (iii) improvement of cellular uptake efficiency. From these achievements, we also discuss the current limitations of mitochondrial transplantation and propose the future direction of the attractive therapeutic methodology.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"107 4","pages":"e70296"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icaritin Inhibits Malignant Progression and Enhances Ferroptosis and Bortezomib Sensitivity by Suppressing HSP90AA1 Expression in Multiple Myeloma.","authors":"Lin Shi, Dianliang Lv, Xueying Wang, Kuanshun Zhang, Lei Feng, Runfang Zhang, Jiangshan Zhao","doi":"10.1111/cbdd.70284","DOIUrl":"10.1111/cbdd.70284","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a hematologic malignancy commonly treated with bortezomib (BTZ). However, treatment efficacy is often limited by the development of BTZ resistance. Icaritin has demonstrated broad anti-tumor activities. This study aimed to investigate the effect of Icaritin on the malignant progression of MM and its potential to overcome BTZ resistance. The anti-MM activity of Icaritin was evaluated through a series of experimental approaches, including cell counting kit 8, flow cytometry, 5-ethynyl-2'-deoxyuridine, network pharmacology, molecule docking, reverse transcription-quantitative polymerase chain reaction, Co-Immunoprecipitation (CoIP), and western blot. Icaritin suppressed MM cell viability and proliferation, induced ferroptosis, and enhanced cellular sensitivity to BTZ. Moreover, Icaritin inhibited HSP90α family 1 (HSP90AA1) protein expression via promoting ubiquitination. HSP90AA1 facilitated MM cell proliferation, suppressed ferroptosis, and attenuated BTZ sensitivity. Notably, Icaritin promoted MM cell ferroptosis and BTZ sensitivity by inhibiting HSP90AA1. In vivo, Icaritin enhanced the sensitivity of tumor cells to BTZ. Icaritin suppresses malignant progression, induces ferroptosis, and enhances BTZ sensitivity in MM by inhibiting HSP90AA1. These findings provide a novel theoretical basis for Icaritin treatment of MM and regulation of BTZ sensitivity.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"107 4","pages":"e70284"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679494","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":"Integrative Multi-Omics Analysis Identifies FTO as a Genetic and Epigenetic Link Between Metabolic Susceptibility and Staphylococcus aureus-Induced Airway Remodeling in Chronic Rhinosinusitis.","authors":"Xinjie Qiao, Dong Dong, Shuman Huang, Yaqian Zhang, Yulin Zhao","doi":"10.1111/cbdd.70297","DOIUrl":"10.1111/cbdd.70297","url":null,"abstract":"<p><p>This study identifies fat mass and obesity-associated protein (FTO) as a pivotal link between metabolic predisposition and pathogenesis associated with Staphylococcus aureus in chronic rhinosinusitis (CRS). These findings were established through the application of an integrative multi-omics framework. We demonstrate that S. aureus upregulates FTO, which functions as an m⁶A demethylase to stabilize the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). This molecular axis suppresses GSK-3β and promotes β-catenin nuclear translocation, thereby driving epithelial-mesenchymal transition (EMT) and pathological mucosal remodeling. By mapping the FTO-MALAT1-GSK-3β/β-catenin signaling network, this research elucidates how metabolic susceptibility facilitates infection-triggered epithelial reprogramming. These findings establish FTO as a promising biomarker and potential therapeutic target, providing a systemic foundation for personalized CRS treatment strategies.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"107 4","pages":"e70297"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679492","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":"Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.","authors":"Terin D'Amico, Tyelor S Reynolds, Michael A Serwetnyk, Brian S J Blagg","doi":"10.1111/cbdd.70290","DOIUrl":"10.1111/cbdd.70290","url":null,"abstract":"<p><p>Recent advances in targeted covalent inhibition have broadened the therapeutic landscape via the development of warheads that target various nucleophilic amino acids. Although cysteine was once the primary focus of such efforts, lysine has emerged as another appealing residue for covalent modification, due to its high prevalence within the proteome, functional importance, and low mutation rate. Despite this amino acid's reduced nucleophilicity at physiological pH, rational, structure-based techniques have enabled the identification of inhibitors that exploit the unique protein microenvironment that a given lysine occupies. Strategies to inhibit Hsp90 via covalent modification of Lys58 include the use of N-acyl-N-aryl sulfonamide (ArNASA) warheads and sulfur(VI) fluoride exchange (SuFEx) chemistry, both of which have demonstrated enhanced cellular selectivity and potency. However, such compounds fail to distinguish between the > 95% identical nature of the ligand binding sites in cytosolic Hsp90α and Hsp90β. In this study, the incorporation of electrophilic warheads onto Hsp90β-selective inhibitors resulted in compounds that demonstrate favorable binding to Hsp90β, yet subsequent analyses to confirm covalent modification of Lys58 were inconclusive. Nevertheless, the kinetics of inhibitor binding to the Hsp90 N-terminal ATP-binding pocket were obtained, whereby some compounds exhibited their highest affinity towards Hsp90β after a 2 h incubation.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"107 4","pages":"e70290"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Biological Assay, and SAR of Potential Anticancer Lipophilic Fluoroquinolones (FQs) and Pyridoquinoxalines (PQs) Conjugated to Gold Nanoparticles for Synergistic and Proapoptogenic Cytotoxicity Drug Design and Targeted Delivery.","authors":"Alaa Tabaza, Yusuf Al-Hiari, Rana Abu-Dahab, Violet Kasabri, Riad Ababneh, Rabab AlBashiti, Ahmad Telfah","doi":"10.1111/cbdd.70128","DOIUrl":"https://doi.org/10.1111/cbdd.70128","url":null,"abstract":"<p><p>In a world where cancer continues to be a major health problem, the urgency continues to find new effective treatments. This work involved the synthesis of more than 10 anticancer fluoroquinolones (FQs) and pyridoquinoxaline (PQ) derivatives originating from FQs and studied their cytotoxicity, anti-adhesion, anti-invasion, and pro-apoptotic properties. Synthesis of the new compounds of the PQ series was carried out by reacting 1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid with L-proline, 3 and 4-hydroxy proline derivatives (compounds 2a-2f), followed by reductive cyclization to yield compounds 3a-3f. Compounds 2a and 3a gave favorable activities on MCF-7 with respective IC₅₀ values of 5.9 and 0.9 μM, respectively, while the hydroxy derivatives almost lost activity on all tested cells. Due to the fact that the activity of PQs and precursor FQs was correlated to increased lipophilicity, the lipophilic FQs series 10a, 10b, 11a, and 11b were prepared by direct reaction of 1-cyclohexyl-6-fluoro-8-nitro-4-oxo-1, 4-dihydroquinoline-3-carboxylate with chloro or fluoro aniline, followed by ester hydrolysis 10a and 10b and reduction to yield the amine compounds 11a and 11b. All FQs 10a, 10b, 11a, and 11b showed very excellent cytotoxicity against all tested cell lines (mammary MCF-7, MDA-MB-231, and invasive prostate DU-145) with IC₅₀ values below 20 μM with impressively favorable lack of any cytotoxicity in normal ligament PDL fibroblasts (in 3.125-200 μM). Only FQs exerted comparable or superior anti-adhesion and anti-invasion activity versus the antineoplastic reference quercetin. Significant incremental increases in the pro-apoptogenesis Bax/anti-apoptosis Bcl ratio revealed a physiologically regulated cytotoxicity via DNA fragmentation harvested in cytolysates. The structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) reveal that planarity due to a fused polycyclic system and lipophilicity were essential requirements for anticancer PQs, whereas a high number of hydrogen bonds (HBs) and increased number of chelators, in addition to lipophilic balance, are the major requirements for anticancer FQs. In vitro cell viability assays revealed pronounced affinity for reductions in cell viabilities for the targeted PQ-bearing AuNPs versus PQsalone (induced) incubations and basal (non-induced) controls after 48 h incubation with HT29 cells. These results are very promising upon optimization of the system.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"106 2","pages":"e70128"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796333","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":"Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis.","authors":"Jingbo Pei, Yuanyuan Zou, Wenying Zhou, Yakun Wang","doi":"10.1111/cbdd.14349","DOIUrl":"10.1111/cbdd.14349","url":null,"abstract":"<p><p>Baicalein, one of the active ingredients of banxia xiexin decoction, has good therapeutic efficacy in treating diarrhea and improving gastrointestinal dysfunction. The role and mechanism of Baicalein on irinotecan (CPT-11)-induced gastrointestinal dysfunction are the focus of this study. Concretely, CPT-11 induced delayed diarrhea rat model and intestinal epithelial cell (IEC)-6 cell injury model with Baicalein treatment as needed. Colonic pathological changes were analyzed by hematoxylin-eosin staining, and inflammatory factor expressions in serum were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and western blot were performed to quantify ferroptosis-related protein expressions. Thiobarbituric acid reactive substances (TBARS) kits and colorimetric assay kit were applied to detect lipid peroxidation levels and Fe²⁺ content, respectively. In vitro experiments also included quantitative real-time polymerase chain reaction, cell counting kit-8, and C11 BODIPY staining. CPT-11 induced aggravation of intestinal tissue damage, inflammatory factor release, Fe²⁺ accumulation, upregulation of lipid peroxidation and 15-Lipoxygenase (ALOX15) expression, and downregulation of glutathione peroxidase 4 (Gpx4) and SLC7A11 in vivo in rats; however, Baicalein dose-dependently reversed the effects of CPT-11. Baicalein elevated cell viability, reduced lipid peroxidation and Fe²⁺ accumulation, and elevated Gpx4 and SLC7A11 levels, whereas ALOX15 overexpression reversed the effects of Baicalein on a CPT-11-induced IEC-6 cell injury model. In conclusion, Baicalein plays a mitigating role in CPT-11-induced delayed diarrhea via ALOX15-mediated ferroptosis.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":" ","pages":"1568-1577"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180705","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":"Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.","authors":"Xinqian He, Yongzhi Sun, Xiaomeng Lu, Fan Yang, Ting Li, Changsheng Deng, Jianping Song, Xin'an Huang","doi":"10.1111/cbdd.14346","DOIUrl":"10.1111/cbdd.14346","url":null,"abstract":"<p><p>Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1β, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":" ","pages":"1534-1552"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165104","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":"Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents","authors":"Oznur Eyilcim,&nbsp;Fulya Gunay,&nbsp;Omer Tahir Gunkara,&nbsp;Yuk Yin Ng,&nbsp;Ozlem Ulucan,&nbsp;Ihsan Erden","doi":"10.1111/cbdd.14328","DOIUrl":"10.1111/cbdd.14328","url":null,"abstract":"<p>A series of novel 1,2,3,4-tetrazines were designed and synthesized. ¹H-NMR spectroscopy, ¹³C NMR spectroscopy, and HRMS were used to determine the structures of this novel compounds. Computational approaches suggested that DHFR is a putative target for the newly synthesized 11 compounds. Extensive molecular dynamics simulations followed by molecular docking simulations were employed to evaluate DHFR as a potential target protein. The anticancer activities of the compounds were evaluated against five different types of leukemia cell lines (Jurkat, Nalm-6, Reh, K562, and Molt-4) and one non-leukemic cell line (Hek293T) by MTT test in vitro and imatinib was used as a control drug. Among these compounds, <b>3a</b> exhibited the best activity against all the leukemic cell lines, except Reh cell line. For Nalm-6, K562, Jurkat, and Molt-4 cell lines, IC₅₀ values were found to be 15.98, 19.12, 23.15, and 25.80 μM, respectively. Our work focuses on the synthesis of original and novel 1,2,3,4-tetrazine derivatives while contributing to the ongoing effort to discover more potent new antileukemia agents.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1186-1201"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180706","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 review of recent advancements in Actinium-225 labeled compounds and biomolecules for therapeutic purposes","authors":"Maria Hassan,&nbsp;Tanveer Hussain Bokhari,&nbsp;Nadeem Ahmed Lodhi,&nbsp;Muhammad Kaleem Khosa,&nbsp;Muhammad Usman","doi":"10.1111/cbdd.14311","DOIUrl":"10.1111/cbdd.14311","url":null,"abstract":"<p>In nuclear medicine, cancers that cannot be cured or can only be treated partially by traditional techniques like surgery or chemotherapy are killed by ionizing radiation as a form of therapeutic treatment. Actinium-225 is an alpha-emitting radionuclide that is highly encouraging as a therapeutic approach and more promising for targeted alpha therapy (TAT). Actinium-225 is the best candidate for tumor cells treatment and has physical characteristics such as high (LET) linear energy transfer (150 keV per μm), half-life (<i>t</i>_1/2 = 9.92d), and short ranges (400–100 μm) which prevent the damage of normal healthy tissues. The introduction of various new radiopharmaceuticals and radioisotopes has significantly assisted the advancement of nuclear medicine. Ac-225 radiopharmaceuticals continuously demonstrate their potential as targeted alpha therapeutics. ²²⁵Ac-labeled radiopharmaceuticals have confirmed their importance in medical and clinical areas by introducing [²²⁵Ac]Ac-PSMA-617, [²²⁵Ac]Ac-DOTATOC, [²²⁵Ac]Ac-DOTA-substance-P, reported significantly improved response in patients with prostate cancer, neuroendocrine, and glioma, respectively. The development of these radiopharmaceuticals required a suitable buffer, incubation time, optimal pH, and reaction temperature. There is a growing need to standardize quality control (QC) testing techniques such as radiochemical purity (RCP). This review aims to summarize the development of the Ac-225 labeled compounds and biomolecules. The current state of their reported resulting clinical applications is also summarized as well.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1276-1292"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261252","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":"Resveratrol alleviates amyloid β-induced neuronal apoptosis, inflammation, and oxidative and endoplasmic reticulum stress by circ_0050263/miR-361-3p/PDE4A axis during Alzheimer's disease","authors":"Yanchun Zhang,&nbsp;Deqiang Chen,&nbsp;Rui Tian,&nbsp;Xinyue Yan,&nbsp;Yingwen Zhou","doi":"10.1111/cbdd.14313","DOIUrl":"10.1111/cbdd.14313","url":null,"abstract":"<p>Resveratrol (Res) has been identified to reduce neurodegeneration. Circular RNAs (circRNAs) are stable noncoding RNAs that are considered to be ideal biomarkers for molecular targeting treatment. Here, this study focused on investigating the function and relationship of circ_0050263 and Res in Alzheimer's Disease (AD). Human neuroblastoma cell line SK-N-SH was exposed to amyloid-β (Aβ) to induce AD cell model in vitro. Cell viability, apoptosis, and inflammatory reaction were evaluated by CCK-8 assay, flow cytometery, and ELISA analysis. The oxidative stress and endoplasmic reticulum stress (ERS) were determined by detecting related markers. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter assay was adopted to verify the binding between miR-361-3p and circ_0050263 or PDE4A (Phosphodiesterase 4A). Subsequently, we found that Res treatment alleviated Aβ-induced apoptosis, inflammatory response, oxidative stress, and ERS in SK-N-SH cells. Circ_0050263 is a stable circRNA, which was increased by Aβ, but decreased by Res in SK-N-SH cells. Circ_0050263 overexpression reversed Res-induced neuroprotective effects. Mechanistically, circ_0050263 acted as a sponge for miR-361-3p, which targeted PDE4A. Circ_0050263 silencing abated Aβ-induced neuronal injury, which were counteracted by following PDE4A overexpression. Moreover, PDE4A upregulation could attenuate Res-mediated neuroprotective effects. In all, Res alleviated Aβ-induced neuronal apoptosis, inflammation, oxidative stress, and ERS via circ_0050263/miR-361-3p/PDE4A axis, providing new insights for AD therapy.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1121-1132"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067200","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}