IUBMB Life最新文献

{"title":"Characterization of a novel heterozygous variant in the histidyl-tRNA synthetase gene associated with Charcot–Marie–Tooth disease type 2W","authors":"Sarah D. P. Wilhelm,&nbsp;Angelica A. Moresco,&nbsp;Alberto D. Rivero,&nbsp;Victoria Mok Siu,&nbsp;Ilka U. Heinemann","doi":"10.1002/iub.2918","DOIUrl":"10.1002/iub.2918","url":null,"abstract":"<p>Heterozygous pathogenic variants in the histidyl-tRNA synthetase (<i>HARS</i>) gene are associated with Charcot–Marie–Tooth (CMT) type 2W disease, classified as an axonal peripheral neuropathy. To date, at least 60 variants causing CMT symptoms have been identified in seven different aminoacyl-tRNA synthetases, with eight being found in the catalytic domain of HARS. The genetic data clearly show a causative role of aminoacyl-tRNA synthetases in CMT; however, the cellular mechanisms leading to pathology can vary widely and are unknown in the case of most identified variants. Here we describe a novel <i>HARS</i> variant, c.412T&gt;C; p.Y138H, identified through a CMT gene panel in a patient with peripheral neuropathy. To determine the effect of p.Y138H we employed a humanized HARS yeast model and recombinant protein biochemistry, which identified a deficiency in protein dimerization and a growth defect which shows mild but significant improvement with histidine supplementation. This raises the potential for a clinical trial of histidine.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1125-1138"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adsorptive removal of naproxen onto nano magnesium oxide-modified castor wood biochar: Treatment of pharmaceutical wastewater via sequential Fenton's-adsorption process","authors":"Amreen Bano,&nbsp;Mohd Kashif Aziz,&nbsp;Fuad Ameen,&nbsp;Kavita Singh,&nbsp;Bablu Prasad,&nbsp; Nandan,&nbsp;Hemen Dave,&nbsp;Rajesh Ravi,&nbsp;Jayanand Manjhi,&nbsp;Madhu Kumari,&nbsp;Kumar Suranjit Prasad","doi":"10.1002/iub.2912","DOIUrl":"10.1002/iub.2912","url":null,"abstract":"<p>This current investigation explored the thermal conversion process of castor wood into biochar, which was subsequently harnessed for removing naproxen from pharmaceutical industrial effluent via adsorption. Surface composition analyses conducted through scanning electron microscopy–energy dispersive X-ray, laser-induced breakdown spectroscopy, and Fourier-transform infrared studies unveiled the presence of nano MgO particles within the adsorbent material. Employing optimization techniques such as response surface methodology facilitated a refined approach to batch study. The optimized conditions for batch naproxen sodium (NPX) adsorption on nano-MgO-modified biochar were identified as pH 4, 1.5 g/L adsorbent dosage, and a 120-min contact time maintaining a constant NPX concentration of 10 mg/L. The adsorption capacity was calculated to be 123.34 mg/g for a nano-magnesium oxide-modified castor wood biochar (modified biochar) and 99.874 mg/g for pristine castor wood biochar (pristine biochar). Fenton's reagents comprising 15 mM of FeSO₄ (7H₂O) and 25 mM of H₂O₂ have been scrutinized under conditions of pH 3.0, a reaction time of 30 min, a temperature of 30°C, and stirring at 120 rpm, followed by batch adsorption treatment. The COD, NH₃–N, NO₃⁻, PO₄³⁻, and NPX removal percentages was found to be 90%, 87%, 79%, 80%, and 90%, respectively. Thus nano MgO-modified biochar holds promise of treatment of pharmaceutical effluent.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1106-1124"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation through naphtho[2,3-a]pyrene on mutated EGFR mediated autophagy in NSCLC: Cellular model system unleashing therapeutic potential","authors":"Nikhil Samarth,&nbsp;Pooja Gulhane,&nbsp;Shailza Singh","doi":"10.1002/iub.2914","DOIUrl":"10.1002/iub.2914","url":null,"abstract":"<p>Mutant epidermal growth factor receptor (EGFR) signaling has emerged as a key cause of carcinogenesis and therapy resistance in non-small cell lung cancer (NSCLC), which continues to pose a serious threat to world health. In this study, we aimed to elucidate the complex molecular pathways of EGFR-mediated autophagy signaling in NSCLC. We identified naphtho[2,3-a]pyrene, an anthraquinolone derivative, to be a promising investigational drug that targets EGFR-mediated autophagy using a cellular model system. By utilizing systems biology, we developed a computational model that explained the signaling of EGFR-mediated autophagy and identified critical crosstalk sites that could be inhibited therapeutically. As a lead compound, naphtho[2,3-a]pyrene was confirmed by molecular docking experiments. It was found to be cytotoxic to NSCLC cells, impact migration, induce apoptosis, and arrest cell cycle, both on its own and when combined with standard drugs. The anticancer efficacy of naphtho[2,3-a]pyrene was validated in vivo on CDX nude mice. It showed synergistic activity against NSCLC when coupled with gefitinib, chloroquine, and radiation. Altogether, our study highlights naphtho[2,3-a]pyrene's therapeutic promise in NSCLC by focusing on EGFR-mediated autophagy and providing a new strategy to fight drug resistance and tumor survival.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1325-1341"},"PeriodicalIF":3.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrimidine–triazole-tethered tert-butyl-piperazine-carboxylate suppresses breast cancer by targeting estrogen receptor signaling and β-catenin activation","authors":"Jie Yuan,&nbsp;Li Yang,&nbsp;Zhi Li,&nbsp;Hua Zhang,&nbsp;Qun Wang,&nbsp;Bei Wang,&nbsp;Arunachalam Chinnathambi,&nbsp;Chandramohan Govindasamy,&nbsp;Shreeja Basappa,&nbsp;Omantheswara Nagaraja,&nbsp;Mahendra Madegowda,&nbsp;Narasimha M. Beeraka,&nbsp;Vladimir N. Nikolenko,&nbsp;Minghua Wang,&nbsp;Geng Wang,&nbsp;Kanchugarakoppal S. Rangappa,&nbsp;Basappa Basappa","doi":"10.1002/iub.2913","DOIUrl":"10.1002/iub.2913","url":null,"abstract":"<p>Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and <i>tert</i>-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial–mesenchymal transition (EMT), possibly via the Wnt/β-catenin pathway.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1309-1324"},"PeriodicalIF":3.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater TIMP-1 protein levels and neointimal formation represent sex-dependent cellular events limiting aortic vessel expansion in female rats","authors":"Aya Al-Katat,&nbsp;Laurie Boudreau,&nbsp;Emmanuelle Gagnon,&nbsp;Ines Assous,&nbsp;Louis Villeneuve,&nbsp;Charles Alexandre Leblanc,&nbsp;Alexandre Bergeron,&nbsp;Martin Sirois,&nbsp;Ismael El-Hamamsy,&nbsp;Angelino Calderone","doi":"10.1002/iub.2916","DOIUrl":"10.1002/iub.2916","url":null,"abstract":"<p>Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl₂ (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl₂-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G₂-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl₂-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl₂-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1356-1376"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSLC4A7 in resistant-cells-derived exosomes promotes docetaxel resistance via the miR-1205/MAPT axis in prostate cancer","authors":"Anhua Lin,&nbsp;Junhe Li,&nbsp;Wenjing He","doi":"10.1002/iub.2915","DOIUrl":"10.1002/iub.2915","url":null,"abstract":"<p>Prostate cancer (PCa) is a high-mortality cancer. Docetaxel (DCT) combined with second-generation anti-androgens is considered the golden standard therapy for PCa, whose application is limited for DCT resistance (DR). Therefore, exploring the mechanism of DR is of great importance. In this study, PCa cell lines of PC3 and DU145 were employed, and DR cells were constructed by treatment with graded DCT. CircSLC4A7, miR-1205, and microtubule-associated protein tau (MAPT) transfections were established. Cell counting kit-8 assay was performed to evaluate the cell activity and IC₅₀ of DCT. After being treated with DCT, DR was assessed by colony formation assay, flow cytometry analysis, and terminal transferase-mediated UTP nick end-labeling assay. Real-time quantitative PCR and western blotting analysis evaluated the expression levels of genes. The dual-luciferase reporter gene assay verified the miR-1205 binding sites with circSLC4A7 and MAPT. An animal experiment was performed to assess the tumor growth influenced by circSLC4A7. After conducting DR cells and isolated exosomes, we found that not only co-culture with DR cells but also treatment with DR cells' exosomes would promote the DR of normal cells. Moreover, circSLC4A7 was highly expressed in DR cells and their exosomes. CircSLC4A7 overexpression enhanced DR, represented as raised IC50 of DCT, increased colony formation, and decreased cell apoptosis after DCT treatment, while circSLC4A7 knockdown had the opposite effect. MiR-1205 was confirmed as a circSLC4A7-sponged miRNA and miR-1205 inhibitor reversed the effect of sh-circSLC4A7. MAPT was further identified as a target of miR-1205 and had a similar effect with circSLC4A7. The effect of circSLC4A7 on DR was also confirmed by xenograft experiments. Collectively, circSLC4A7 in resistant-cells-derived exosomes promotes DCT resistance of PCa via miR-1205/MAPT axis, which may provide a new treatment strategy for DR of PCa.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1342-1355"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNHG14 promotes triple-negative breast cancer cell proliferation, invasion, and chemoresistance by regulating the ERK/MAPK signaling pathway","authors":"Bin Wang,&nbsp;Ai-Yan Xing,&nbsp;Guang-Xin Li,&nbsp;Long Liu,&nbsp;Chungen Xing","doi":"10.1002/iub.2910","DOIUrl":"10.1002/iub.2910","url":null,"abstract":"<p>The functional role and molecular mechanisms of small-nucleolar RNA host gene 14 (SNHG14) in triple-negative breast cancer (TNBC) progression remain unclear. The expression levels of SNHG14 in breast cancer samples and cell lines were determined using real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion abilities were detected using MTS and transwell assays. By RNA sequencing, differentially expressed genes were identified between the SNHG14 siRNA and the negative control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to predict the targets and pathways regulated by SNHG14. pRAF, pMEK, and pERK expression were measured by western blot. The xenograft model was constructed to access the biological function of SNHG14 in vivo. A minimal patient-derived xenograft model was established to evaluate the sensitivity to chemotherapy drugs. Our data indicated that SNHG14 expression was increased in TNBC tissues and cell lines. SNHG14 knockdown attenuated the proliferation, migration, and invasion abilities of TNBC cells both in vivo and in vitro. High SNHG14 expression was associated with lymph node metastasis and a high Ki67 index. The targets of SNHG14 were mainly enriched in the MAPK signaling pathway. pRAF, pMEK, and pERK expression were downregulated after being transfected with SNHG14 siRNA. Compared with the negative control group, the expression of CACNA1I, DUSP8, FGF17, FGFR4, FOS, PDGFRB, and DDIT3 was increased, and the expression of MKNK1 was decreased in the SNHG14 siRNA group. Minimal patient-derived xenograft model demonstrated that knockdown of SNHG14 enhanced the sensitivity to Docetaxel in vivo. Compared with the DMSO group, the proliferation of Docetaxel-resistant MDA-MB-231 cells was decreased in Dabrafenib, PD184352, and FR180204 treatment groups. SNHG14 knockdown inhibits TNBC progression by regulating the ERK/MAPK signaling pathway, which provides evidence for SNHG14 as a potential target for TNBC therapy.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1295-1308"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiouracil and triazole conjugate induces autophagy through the downregulation of Wnt/β-catenin signaling pathway in human breast cancer cells","authors":"Bada Yoon,&nbsp;Basappa Basappa,&nbsp;Shreeja Basappa,&nbsp;Omantheswara Nagaraju,&nbsp;Mahendra Madegowda,&nbsp;K. S. Rangappa,&nbsp;Gautam Sethi,&nbsp;Kwang Seok Ahn","doi":"10.1002/iub.2917","DOIUrl":"10.1002/iub.2917","url":null,"abstract":"<p>Autophagy is vital for maintaining cellular homeostasis by breaking down unnecessary organelles and proteins within cells. Its activity varies abnormally in several diseases, including cancer, making it a potential target for therapeutic strategies. The Wnt/β-catenin signaling pathway significantly impacts cancer by stabilizing β-catenin protein and promoting the transcription of its target genes. Therefore, we aimed to identify candidate substances targeting this signaling pathway. We designed and tested a thiouracil conjugate, discovering that TTP-8 had anti-tumor effects on human breast cancer cell lines MCF-7 and MDA-MB231. Our findings showed that TTP-8 upregulated the expression of LC3 protein, a marker of autophagy in breast cancer cells, suggesting that TTP-8 might induce autophagy. Further analysis confirmed an increase in autophagy-related proteins, with consistent results obtained from flow cytometry and confocal microscopy. Interestingly, the induction of LC3 expression by TTP-8 was even more pronounced in MCF-7 and MDA-MB231 cells transfected with β-catenin siRNA. Thus, our research supports the idea that the Wnt/β-catenin signaling pathway influences the regulation of autophagy-related proteins, thereby inducing autophagy. This suggests that TTP-8 could serve as a novel agent for treating breast cancer.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1377-1391"},"PeriodicalIF":3.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AARS Online: A collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases","authors":"Jordan Douglas,&nbsp;Haissi Cui,&nbsp;John J. Perona,&nbsp;Oscar Vargas-Rodriguez,&nbsp;Henna Tyynismaa,&nbsp;Claudia Alvarez Carreño,&nbsp;Jiqiang Ling,&nbsp;Lluís Ribas de Pouplana,&nbsp;Xiang-Lei Yang,&nbsp;Michael Ibba,&nbsp;Hubert Becker,&nbsp;Frédéric Fischer,&nbsp;Marie Sissler,&nbsp;Charles W. Carter Jr,&nbsp;Peter R. Wills","doi":"10.1002/iub.2911","DOIUrl":"10.1002/iub.2911","url":null,"abstract":"<p>The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1091-1105"},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function","authors":"Ting Yang,&nbsp;Yan Tang,&nbsp;Xinghua Liu,&nbsp;Song Gong,&nbsp;Ensheng Yao","doi":"10.1002/iub.2903","DOIUrl":"10.1002/iub.2903","url":null,"abstract":"<p>Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1209-1222"},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}