Cell Death Discovery最新文献

DUBs in Alzheimer's disease: mechanisms and therapeutic implications. 阿尔茨海默病中的 DUBs：机制和治疗意义。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-20 DOI: 10.1038/s41420-024-02237-3

Biying Qin, Xiaodong Chen, Feng Wang, Yanfeng Wang

{"title":"DUBs in Alzheimer's disease: mechanisms and therapeutic implications.","authors":"Biying Qin, Xiaodong Chen, Feng Wang, Yanfeng Wang","doi":"10.1038/s41420-024-02237-3","DOIUrl":"https://doi.org/10.1038/s41420-024-02237-3","url":null,"abstract":"Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by the accumulation of amyloid β protein (Aβ) and the hyper-phosphorylation of the microtubule-associated protein Tau. The ubiquitin-proteasome system (UPS) plays a pivotal role in determining the fate of proteins, and its dysregulation can contribute to the buildup of Aβ and Tau. Deubiquitinating enzymes (DUBs), working in conjunction with activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3), actively maintain the delicate balance of protein homeostasis. DUBs specifically remove ubiquitin tags from proteins marked for degradation, thereby averting their proteasomal breakdown. Several DUBs have demonstrated their capacity to regulate the levels of Aβ and Tau by modulating their degree of ubiquitination, underscoring their potential as therapeutic targets for AD. In this context, we present a comprehensive review of AD-associated DUBs and elucidate their physiological roles. Moreover, we delve into the current advancements in developing inhibitors targeting these DUBs, including the determination of cocrystal structures with their respective targets. Additionally, we assess the therapeutic efficacy of these inhibitors in AD, aiming to establish a theoretical foundation for future AD treatments.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"475"},"PeriodicalIF":6.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms. 人类原始多能性和原始多能性重编程过程中的染色质景观动态揭示了 PRDM1 同工型的不同功能。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-19 DOI: 10.1038/s41420-024-02230-w

Jianfeng Zhou, Mingyue Guo, Guang Yang, Xinyu Cui, Jindian Hu, Tan Lin, Hong Wang, Shaorong Gao, Cizhong Jiang, Liping Wang, Yixuan Wang

{"title":"Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms.","authors":"Jianfeng Zhou, Mingyue Guo, Guang Yang, Xinyu Cui, Jindian Hu, Tan Lin, Hong Wang, Shaorong Gao, Cizhong Jiang, Liping Wang, Yixuan Wang","doi":"10.1038/s41420-024-02230-w","DOIUrl":"https://doi.org/10.1038/s41420-024-02230-w","url":null,"abstract":"Induced pluripotent stem cells (iPSCs) technology holds great potential in both scientific research and clinical applications. It enables the generation of naïve and primed iPSCs from various cell types through different strategies. Despite extensive characterizations of transcriptional and epigenetic factors, the intricacies of chromatin landscape dynamics during naïve and primed reprogramming, particularly in humans, remain poorly understood. In this study, we employed ATAC-seq and RNA-seq analyses to delineate and compare the chromatin landscape of naïve and primed pluripotency through the human secondary reprogramming system. Our investigations revealed several key transcriptional and epigenetic factors pivotal for reprogramming-associated chromatin remodeling. Notably, we found two isoforms of PRDM1, PRDM1α, and PRDM1β, bind to distinct genomic loci and play different roles in the naïve reprogramming process. We proposed an auto-regulatory model explaining the distinct functions of PRDM1α and PRDM1β. Overall, our findings highlight the complexity and diversity of transcription factors in shaping chromatin landscape dynamics and directing the fates of pluripotent cells.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"474"},"PeriodicalIF":6.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination. NEDD4L 通过促进 xCT 泛素化，有助于食管鳞状细胞癌的铁变态和细胞生长抑制。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-18 DOI: 10.1038/s41420-024-02243-5

Zhen Chen, Weilong Wang, Jinghan Hou, Can Gao, Meili Song, Zijun Zhao, Ruirui Guan, Jingsheng Chen, Huicheng Wu, Siti Razila Abdul Razak, Tao Han, Junbo Zhang, Lidong Wang, Nor Hazwani Ahmad, Xiumin Li

{"title":"NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination.","authors":"Zhen Chen, Weilong Wang, Jinghan Hou, Can Gao, Meili Song, Zijun Zhao, Ruirui Guan, Jingsheng Chen, Huicheng Wu, Siti Razila Abdul Razak, Tao Han, Junbo Zhang, Lidong Wang, Nor Hazwani Ahmad, Xiumin Li","doi":"10.1038/s41420-024-02243-5","DOIUrl":"10.1038/s41420-024-02243-5","url":null,"abstract":"The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"473"},"PeriodicalIF":6.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic advances in the targeting of ROR1 in hematological cancers. 针对血液肿瘤中 ROR1 的治疗进展。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-17 DOI: 10.1038/s41420-024-02239-1

Adrian-Bogdan Tigu, Raluca Munteanu, Cristian Moldovan, Drula Rares, David Kegyes, Radu Tomai, Vlad Moisoiu, Gabriel Ghiaur, Ciprian Tomuleasa, Hermann Einsele, Diana Gulei, Carlo M Croce

{"title":"Therapeutic advances in the targeting of ROR1 in hematological cancers.","authors":"Adrian-Bogdan Tigu, Raluca Munteanu, Cristian Moldovan, Drula Rares, David Kegyes, Radu Tomai, Vlad Moisoiu, Gabriel Ghiaur, Ciprian Tomuleasa, Hermann Einsele, Diana Gulei, Carlo M Croce","doi":"10.1038/s41420-024-02239-1","DOIUrl":"10.1038/s41420-024-02239-1","url":null,"abstract":"Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies. The development of ROR1 targeted therapies is continuously growing leading to remarkable novel therapeutical approaches using mAbs, antibody-drug conjugates, several small molecules or CAR T cells which have shown encouraging preclinical results. In the hematological field, mAbs, small molecules, BiTEs or CAR T cell therapies displayed promising outcomes with the clinical trials data encouraging the use of anti-ROR1 therapies. This paper aims to offer a comprehensive analysis of the current landscape of ROR1-targeted therapies in hematological malignancies marking the innovative approaches with promising preclinical and clinical. Offering a better understanding of structural and functional aspects of ROR1 could lead to new perspectives in targeting a wide spectrum of malignancies.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"471"},"PeriodicalIF":6.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DDX3 is critical for female fertility via translational control in oogenesis. DDX3 在卵子生成过程中通过翻译控制对雌性生育能力至关重要。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-17 DOI: 10.1038/s41420-024-02242-6

Shang-Yu Tsai, Chih-Hung Lin, Yu-Ting Jiang, Guo-Jen Huang, Haiwei Pi, Hsin-Yuan Hung, Woan-Yuh Tarn, Ming-Chih Lai

{"title":"DDX3 is critical for female fertility via translational control in oogenesis.","authors":"Shang-Yu Tsai, Chih-Hung Lin, Yu-Ting Jiang, Guo-Jen Huang, Haiwei Pi, Hsin-Yuan Hung, Woan-Yuh Tarn, Ming-Chih Lai","doi":"10.1038/s41420-024-02242-6","DOIUrl":"10.1038/s41420-024-02242-6","url":null,"abstract":"DEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"472"},"PeriodicalIF":6.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Broad-spectrum inflammasome inhibition by thiomuscimol. 硫代麝香草酚的广谱炎症小体抑制作用

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-16 DOI: 10.1038/s41420-024-02238-2

Marisa J Anderson, Andreas B den Hartigh, Wendy P Loomis, Susan L Fink

{"title":"Broad-spectrum inflammasome inhibition by thiomuscimol.","authors":"Marisa J Anderson, Andreas B den Hartigh, Wendy P Loomis, Susan L Fink","doi":"10.1038/s41420-024-02238-2","DOIUrl":"10.1038/s41420-024-02238-2","url":null,"abstract":"Inflammasome formation, arising from pathogen or internal activating signals, is a key step in canonical pyroptosis, a gasdermin-mediated inflammatory cell death. Inhibition of pyroptosis has great clinical relevance due to its involvement in many different disease states. Current inhibitors of pyroptosis either only inhibit the final lytic step, which still allows inflammatory signal release, or only inhibit a single inflammasome, which does not account for inherent redundancy in activation of other inflammatory pathways. Here, we show that thiomuscimol, a structural analog of the lysis inhibitor muscimol, exhibits unique inhibitory activity upstream of plasma membrane rupture. We find that thiomuscimol inhibits inflammasome formation, as well as downstream caspase-1 activation, initiated by multiple pyroptotic signals, regardless of whether NLR recruitment of caspase-1 to the inflammasome relies on the ASC adapter protein. The ability of thiomuscimol to block multiple different inflammasomes opens the door for development of therapeutics with increased applications to broadly inhibit pyroptosis in multiple pathological settings.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"470"},"PeriodicalIF":6.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of PDLIM1 as a glioblastoma stem cell marker driving tumorigenesis and chemoresistance. 鉴定 PDLIM1 为胶质母细胞瘤干细胞标记物，可驱动肿瘤发生和化疗抗药性。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-15 DOI: 10.1038/s41420-024-02241-7

Xiaopeng Shen, Yun Zhao, Yang Cao, Yunfeng Liu, Jian Ruan, Chunguang Wang, Meng Li, Huaizhang Jin, Shan Lu, Guoping Zhu

{"title":"Identification of PDLIM1 as a glioblastoma stem cell marker driving tumorigenesis and chemoresistance.","authors":"Xiaopeng Shen, Yun Zhao, Yang Cao, Yunfeng Liu, Jian Ruan, Chunguang Wang, Meng Li, Huaizhang Jin, Shan Lu, Guoping Zhu","doi":"10.1038/s41420-024-02241-7","DOIUrl":"10.1038/s41420-024-02241-7","url":null,"abstract":"Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, largely due to the presence of glioblastoma stem cells (GSCs). These cells drive tumor progression, recurrence, and chemoresistance, making them critical targets for therapy. This study aims to identify novel GSC markers for improved diagnosis and targeted treatment. We utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify PDLIM1 as a novel GSC marker. PDLIM1 was specifically expressed in GSCs and was associated with poor prognosis and advanced tumor stages. Functional assays demonstrated that PDLIM1 overexpression enhanced GBM cell proliferation, reduced apoptosis, increased GSC proportions, and promoted chemoresistance and tumorigenesis. Conversely, PDLIM1 knockdown inhibited these processes. Mechanistically, PDLIM1 was found to exert its effects likely by promoting the PI3K-AKT pathway. In conclusion, PDLIM1 may serve as a potential marker of GSCs associated with poor prognosis, tumorigenesis, and chemoresistance in GBM, representing a potential therapeutic target for improving GBM patient outcomes.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"469"},"PeriodicalIF":6.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome. 鉴定特纳综合征人类 iPSC 衍生颗粒细胞模型中的凋亡素/APJ 信号失调。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-14 DOI: 10.1038/s41420-024-02231-9

Wei-Ju Chen, Yi-Ya Chao, Wei-Kai Huang, Wei-Fang Chang, Chii-Ruey Tzeng, Chi-Hsuan Chuang, Pei-Lun Lai, Scott C Schuyler, Long-Yuan Li, Jean Lu

{"title":"Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome.","authors":"Wei-Ju Chen, Yi-Ya Chao, Wei-Kai Huang, Wei-Fang Chang, Chii-Ruey Tzeng, Chi-Hsuan Chuang, Pei-Lun Lai, Scott C Schuyler, Long-Yuan Li, Jean Lu","doi":"10.1038/s41420-024-02231-9","DOIUrl":"10.1038/s41420-024-02231-9","url":null,"abstract":"The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly affects females who have a partial or complete loss of one X chromosome. Our understanding of the role that granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. In this study, we achieved GC differentiation efficiency of up to 80% from iPSCs. When attempting to replicate the differentiation process of embryonic granulosa cells, we observed the downregulation of specific genes-GATA4, FOXL2, AMHR2, CYP19A1, and FSH-in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, we identified dysregulation of the cell cycle in TS-GCs. To uncover the endogenous defects in TS-GCs, we compared global transcriptome patterns between iPSC-derived granulosa cells from healthy individuals and those with Turner syndrome. The apelin/APJ pathway exhibited differential signaling between the healthy and TS groups. Supplementation with apelin ligands and activation of apelin/APJ downstream signaling via Akt/PKB restored cell cycle progression and marker gene expression. We hypothesize that during early embryonic development, failures in apelin/APJ signaling in GCs of Turner syndrome patients lead to abnormalities in ovarian development, ultimately resulting in early oocyte loss and infertility.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"468"},"PeriodicalIF":6.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N-Acetylneuraminic acid triggers endothelial pyroptosis and promotes atherosclerosis progression via GLS2-mediated glutaminolysis pathway. N-乙酰神经氨酸通过 GLS2 介导的谷氨酰胺溶解途径引发内皮细胞热解并促进动脉粥样硬化的进展。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-13 DOI: 10.1038/s41420-024-02233-7

Zhaohong Liu, Peng Xiang, Shengmei Zeng, Ping Weng, Yilin Wen, Wanping Zhang, Hui Hu, Dezhang Zhao, Limei Ma, Chao Yu

{"title":"N-Acetylneuraminic acid triggers endothelial pyroptosis and promotes atherosclerosis progression via GLS2-mediated glutaminolysis pathway.","authors":"Zhaohong Liu, Peng Xiang, Shengmei Zeng, Ping Weng, Yilin Wen, Wanping Zhang, Hui Hu, Dezhang Zhao, Limei Ma, Chao Yu","doi":"10.1038/s41420-024-02233-7","DOIUrl":"10.1038/s41420-024-02233-7","url":null,"abstract":"Vascular endothelial injury initiates atherosclerosis (AS) progression. N-Acetylneuraminic acid (Neu5Ac) metabolic disorder was found to intensify endothelial mitochondrial damage. And GLS2-associated glutaminolysis disorder contributed to mitochondrial dysfunction. However, mechanisms underlying Neu5Ac-associated mitochondrial dysfunction as well as its association with GLS2 remains unclear. In this study, we constructed GLS2-/-ApoE-/- mice by using HBLV-GLS2 shRNA injection. And methods like immunofluorescence, western blotting, transmission electron microscopy were applied to detect profiles of endothelial injury and AS progression both in vivo and in vitro. We demonstrated that Neu5Ac accumulation increased GLS2 expression and promoted glutaminolysis disorder, which further induced endothelial mitochondrial dysfunction via a pyroptosis-dependent pathway in vivo and in vitro. Mechanically, Neu5Ac interacted with SIRT3 and led to FOXO3a deacetylation and phosphorylation, further facilitated c-Myc antagonism and ultimately increased GLS2 levels. Inhibition of GLS2 could improve mitochondrial function and mitigate pyroptosis process. In addition, blocking Neu5Ac production using neuraminidases (NEUs) inhibitor could rescue endothelial damage and alleviate AS development in ApoE-/- mice. These findings proposed that Neu5Ac induced GLS2-mediated glutaminolysis disorder and then promoted mitochondrial dysfunction in a pyroptosis-dependent pathway. Targeting GLS2 or inhibiting Neu5Ac production could prevent AS progression.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"467"},"PeriodicalIF":6.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in smart nanotechnology-supported photodynamic therapy for cancer. 智能纳米技术支持的癌症光动力疗法的进展。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-11-11 DOI: 10.1038/s41420-024-02236-4

Guangyao Li, Cong Wang, Binghui Jin, Tao Sun, Kang Sun, Shuang Wang, Zhe Fan

{"title":"Advances in smart nanotechnology-supported photodynamic therapy for cancer.","authors":"Guangyao Li, Cong Wang, Binghui Jin, Tao Sun, Kang Sun, Shuang Wang, Zhe Fan","doi":"10.1038/s41420-024-02236-4","DOIUrl":"10.1038/s41420-024-02236-4","url":null,"abstract":"Cancer has emerged as a formidable challenge in the 21st century, impacting society, public health, and the economy. Conventional cancer treatments often exhibit limited efficacy and considerable side effects, particularly in managing the advanced stages of the disease. Photodynamic therapy (PDT), a contemporary non-invasive therapeutic approach, employs photosensitizers (PS) in conjunction with precise light wavelengths to selectively target diseased tissues, inducing the generation of reactive oxygen species and ultimately leading to cancer cell apoptosis. In contrast to conventional therapies, PDT presents a lower incidence of side effects and greater precision in targeting. The integration of intelligent nanotechnology into PDT has markedly improved its effectiveness, as evidenced by the remarkable synergistic antitumor effects observed with the utilization of multifunctional nanoplatforms in conjunction with PDT. This paper provides a concise overview of the principles underlying PS and PDT, while also delving into the utilization of nanomaterial-based PDT in the context of cancer treatment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"466"},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0