Apoptosis最新文献

{"title":"Endothelial HMGB1-AIM2 axis worsens myocardial ischemia—reperfusion injury by regulating endothelial pyroptosis","authors":"Rui Chen,&nbsp;Junying Duan,&nbsp;Ye Zhou,&nbsp;Mengfei Cao,&nbsp;Ye Su,&nbsp;Duzhe Jiang,&nbsp;Aibin Tao,&nbsp;Wei Yuan,&nbsp;Zhiying Dai","doi":"10.1007/s10495-025-02162-5","DOIUrl":"10.1007/s10495-025-02162-5","url":null,"abstract":"<div><p>This study investigates mechanisms related to endothelial cells in myocardial ischaemia–reperfusion (I/R) injury, focusing on the role of high-mobility group box 1 (HMGB1) protein in these cells. Using a murine model, we observed elevated levels of HMGB1 in both the heart and circulation following I/R, with a portion originating from cardiac vascular endothelial cells and cardiomyocytes. Endothelial cell-specific HMGB1 knockout preserved cardiac function after I/R by reducing infarct size, mitigating myocardial damage, maintaining endothelial cell barrier function, and attenuating inflammatory and oxidative stress responses. Single-cell analysis revealed that HMGB1 endothelial knockout altered cardiac cell composition by decreasing the proportion of endothelial cells with high fatty acid-binding protein 4 expression. Mechanistically, HMGB1 endothelial knockout significantly inhibited the expression of absent in melanoma 2 (AIM2)-associated inflammasome- and pyroptosis-related proteins after I/R, whereas AIM2 overexpression exacerbated myocardial injury, inflammation, and the expression of pyroptosis-related proteins. Our findings demonstrate that the endothelial HMGB1-AIM2 axis worsens I/R injury by regulating endothelial cell pyroptosis, suggesting a novel pathway involved in microcirculatory dysfunction during myocardial I/R injury.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2466 - 2479"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854307","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}

{"title":"Pyroptosis: inflammatory cell death mechanism and its pathological roles in neurological diseases and injuries","authors":"Haonan Ma,&nbsp;Yapei Zhu,&nbsp;Xuan Zhao,&nbsp;Liujiangshan Jiang,&nbsp;Jing Yang,&nbsp;Tianyao Yang,&nbsp;Wei Liu","doi":"10.1007/s10495-025-02160-7","DOIUrl":"10.1007/s10495-025-02160-7","url":null,"abstract":"<div><p>Neurological disorders represent a major global public health challenge, causing significant impairments in motor, sensory, and cognitive functions. Among these disorders, Alzheimer’s disease, cerebrovascular diseases, and Parkinson’s disease are notably prevalent. Despite their widespread impact, effective therapeutic interventions remain limited. Recently, pyroptosis—a highly pro-inflammatory form of programmed cell death characterized by cell swelling, membrane perforation, and the release of cellular contents—has gained considerable attention. While pyroptosis plays a crucial role in host defense against pathogen infections, its excessive activation can trigger sustained inflammatory responses and has been implicated in the pathogenesis and progression of various neurological disorders. This review provides an overview of pyroptosis, including its definition, key molecular components, and associated signaling pathways, while examining its mechanistic roles in neuroinflammation, neurological disorders, cerebrovascular diseases, and neural tumors. Additionally, it explores the influence of other systemic dysregulations on the development of neurological disorders. Research has demonstrated that pyroptosis drives the death of neurons and glial cells through inflammasome activation and the Caspase-Gasdermin pathway, thereby amplifying neuroinflammation and influencing disease progression. Notably, excessive pyroptosis activation exacerbates neural damage in conditions such as Alzheimer’s disease, Parkinson’s disease, and ischemic brain injury. Consequently, targeting pyroptosis signaling pathways may present promising therapeutic strategies for neurological disorders. This review consolidates recent advancements in the field, offering valuable insights for the development of effective interventions.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2057 - 2076"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854323","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}

{"title":"Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy","authors":"Fei Xiao,&nbsp;Hui-Li Li,&nbsp;Jia-Rui Wang,&nbsp;Hui-Min Wu,&nbsp;Yu-Qi Cai,&nbsp;Jia-Wan Wang,&nbsp;Hao Che,&nbsp;Gang Li,&nbsp;Zheng-Yuan Xia,&nbsp;Yu-Bo Xie,&nbsp;Sheng Wang","doi":"10.1007/s10495-025-02146-5","DOIUrl":"10.1007/s10495-025-02146-5","url":null,"abstract":"<div><p>Pressure overload hypertrophic cardiomyopathy (PO-HCM), a prevalent cardiovascular condition, is characterized by the heart’s adaptive response to chronic pressure overload. However, excessive pressure overload contributes to cardiomyocyte dysfunction and pathological hypertrophy. The pathological hallmarks of PO-HCM include the abnormal enlargement of cardiomyocytes (hypertrophy) and structural remodeling of myocardial tissue. The pathogenesis is multifaceted and involves hemodynamic alterations, imbalances in neurohumoral regulation, and intracellular signaling pathway abnormalities. Within this pathological context, programmed cell death is critically involved in cardiomyocytes. This review synthesizes current research on programmed cell death mechanisms in PO-HCM—including apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis—to inform translational research and guide future therapeutic development.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2191 - 2224"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02146-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854324","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}

{"title":"Emerging role of RNA m6A modifications in laryngeal squamous cell carcinoma: insights into tumorigenesis and therapeutic potential","authors":"Guotong Zheng,&nbsp;Jing Bi,&nbsp;Yangyan Yan,&nbsp;Bo Yu,&nbsp;Yong Fu","doi":"10.1007/s10495-025-02159-0","DOIUrl":"10.1007/s10495-025-02159-0","url":null,"abstract":"<div><p>Laryngeal squamous cell carcinoma (LSCC) is one of the major malignant cancers worldwide. Emerging evidence has demonstrated that N6-methyladenosine (m6A) modification affects gene expression by regulating RNA metabolic processes, dynamically and reversibly regulated by its “writers”, “erasers” and “readers”. m6A modification plays an important role in the occurrence and development of various tumors. Recent studies have shown that m6A modifications are abnormally expressed in LSCC cells and tissues and participate in the malignant phenotypes of LSCC including cell proliferation, invasion, metastasis and chemotherapy resistance by mediating m6A regulators. This fundings may provide new directions for the molecular classification and targeted treatment of LSCC. In this review, we will focus on the molecular mechanism and potential clinical function of m6A modification in LSCC and emphasize its potential as a biomarker for the clinical diagnosis, prognosis, and treatment of LSCC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2077 - 2089"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854306","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}

{"title":"GSDME-dependent astrocyte pyroptosis promotes the progression of neuroinflammation in experimental cerebral malaria","authors":"Jun Wang,&nbsp;Qinghao Zhu,&nbsp;Guodong Tong,&nbsp;Kangjie Yu,&nbsp;Jiao Liang,&nbsp;Yuxiao Huang,&nbsp;Yi Wang,&nbsp;Chao Yang,&nbsp;Tong Li,&nbsp;Weilu Liang,&nbsp;Ganze Li,&nbsp;Xiaoran Liu,&nbsp;Jiayi Sun,&nbsp;Yinghui Li,&nbsp;Yan Shen,&nbsp;Ya Zhao","doi":"10.1007/s10495-025-02140-x","DOIUrl":"10.1007/s10495-025-02140-x","url":null,"abstract":"<div><p>\u0000 Cerebral malaria (CM), a life-threatening neurological complication of <i>Plasmodium falciparum</i> infection, is characterized by severe neuroinflammation and long-term neurological sequelae. Central nervous system inflammation, driven by brain-infiltrated CD8⁺ T cells, represents a hallmark pathological feature of CM. In this study, we demonstrate that astrocytes, a critical component of the blood–brain barrier and neurovascular unit, exhibit a robust interferon-γ response during CM, facilitating CD8⁺ T cell recruitment into the brain parenchyma and antigen presentation to these immune cells. Importantly, we identify gasdermin E (GSDME)-dependent pyroptosis in astrocytes, a process triggered by brain-infiltrated CD8⁺ T cells. This pyroptotic pathway amplifies neuroinflammation and exacerbates neuronal injury. Genetic ablation of <i>Gsdme</i> or pharmacological inhibition of GSDME activation by mannose significantly attenuated brain inflammation and damage in a murine CM model. Our findings establish, for the first time, that GSDME-dependent astrocyte pyroptosis critically exacerbates neuroinflammation in CM. These results highlight GSDME as a novel therapeutic target for mitigating CM and related neuroinflammatory diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2385 - 2400"},"PeriodicalIF":8.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854322","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}

{"title":"Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.","authors":"Md Jakaria, Jason R Cannon","doi":"10.1007/s10495-025-02156-3","DOIUrl":"10.1007/s10495-025-02156-3","url":null,"abstract":"<p><p>Neuromelanin is a complex dark brown pigment that primarily accumulates in catecholaminergic neurons, particularly in the substantia nigra and locus coeruleus regions of the brain in primates. Rats and mice are largely devoid of neuromelanin, although it is present in some other non-primate species. This pigment is notable for its age-related accumulation and has been linked to the pathophysiology of various neurodegenerative diseases, especially Parkinson's disease. Research has increasingly suggested that neuromelanin or its precursors trigger cellular stress, including neuroinflammation, apoptosis, oxidative stress, mitochondrial dysfunction, and impaired autophagy. Collectively, these mechanisms significantly contribute to neurodegeneration. Additionally, neuromelanin can interact with various neurotoxic molecules, potentially forming complexes that may provide protective benefits against neurotoxicity. However, extensive studies also suggest that this interaction can have a double-edged effect; while it may sequester harmful substances, it can simultaneously increase cellular stress and enhance neuronal toxicity, creating a detrimental cycle. We review the multifaceted roles of neuromelanin in the brain, discussing how its properties and interactions contribute to cellular stress and the progression of neurodegenerative processes. In the context of neurotoxic mechanisms, we also address potential therapeutic targets for Parkinson's disease.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798030","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}

{"title":"Targeting cuproptosis in liver cancer: Molecular mechanisms and therapeutic implications","authors":"Yun-Fei Zhou,&nbsp;Yi-Wen Zhu,&nbsp;Meng-Yuan Hao,&nbsp;Hong-Jie Li,&nbsp;Hang-Shen Han,&nbsp;Yan-Ge Li,&nbsp;Wei-Rong Si,&nbsp;Qi-Ying Jiang,&nbsp;Dong-Dong Wu","doi":"10.1007/s10495-025-02150-9","DOIUrl":"10.1007/s10495-025-02150-9","url":null,"abstract":"<div><p>Liver cancer (LC) stands as one of the most prevalent and highly malignant tumors globally, with persistently elevated mortality rates. For advanced-stage LC, identifying efficacious treatment modalities remains a critical imperative. Cuproptosis, a newly identified form of regulated cell death, exhibits therapeutic potential for impeding LC progression. However, the current clinical evidence remains limited, meriting further in-depth investigation by researchers. Existing literature has summarized copper homeostasis, the molecular mechanisms of cuproptosis, and its roles in certain cancers. However, key challenges in clinical translation haven’t been included in the research scope, such as the mechanistic complexity, poor targeting specificity, lack of mature biomarkers, and risk of therapeutic resistance. Notably, the lessons from failed clinical trials have not been fully integrated into ongoing investigations. This review systematically delineates cuproptosis-associated biomarkers in LC, critically analyzes the challenges of targeting cuproptosis for LC therapy and discusses potential solutions. By highlighting current research gaps, we aim to provide actionable research directions for future investigations.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2163 - 2190"},"PeriodicalIF":8.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798031","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}

{"title":"Mitochondrial bioenergetics and networks in melanoma: an update","authors":"Gaia Giannitti,&nbsp;Alyssa Julia Jennifer Paganoni,&nbsp;Sara Marchesi,&nbsp;Riccardo Garavaglia,&nbsp;Fabrizio Fontana","doi":"10.1007/s10495-025-02155-4","DOIUrl":"10.1007/s10495-025-02155-4","url":null,"abstract":"<div><p>Melanoma is the most aggressive and deadly form of skin cancer. However, advances in the understanding of its biology have led to the development of several new therapeutic approaches. One of these novel treatment strategies is based on the targeting of the mitochondrial bioenergetic and networks responsible for tumor initiation and progression. Indeed, it has recently emerged that changes in mitochondrial metabolism, dynamics, redox homeostasis, and apoptosis are strictly associated with tumor growth, metastasis, and drug resistance. In this review, we summarize current evidence about the multiple biological functions exerted by mitochondria in melanoma, also focusing on the role of these organelles as promising targets for pharmacological intervention.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2042 - 2056"},"PeriodicalIF":8.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02155-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726871","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}

{"title":"Novel L-type chiral metal(II) complexes inhibit breast cancer growth through synergistic effects of anti-angiogenesis, anti-inflammatory, apoptosis induction and cuproptosis","authors":"Nan Jin,&nbsp;Bing-Bing Xu,&nbsp;Hong-Yu Lin,&nbsp;Bing-Li Jiang,&nbsp;Qiao-Ying Yang,&nbsp;Xiu-Ying Qin","doi":"10.1007/s10495-025-02149-2","DOIUrl":"10.1007/s10495-025-02149-2","url":null,"abstract":"<div><p>Breast cancer ranks first among female malignant tumors and is the largest cancer worldwide. Recently, research on chiral metal-based complexes for cancer treatment has significantly increased. This study synthesized an <i>L</i>-copper(II) complex Cu-1 and a pair of chiral nickel(II) complexes Ni-1 (<i>L</i>-type) and Ni-2 (<i>D</i>-type). The antiproliferative activities of Cu-1, Ni-1, and Ni-2 against female malignant tumor cells (MCF-7, MDA-MB-231, SKOV3, Hela) were evaluated. Among them, the <i>L</i>-type complexes Cu-1 and Ni-1 exhibited superior bioactivity compared to the <i>D</i>-type Ni-2. Further mechanistic studies demonstrated that Cu-1 and Ni-1 could effectively inhibit the growth of MCF-7 cells. Additionally, in vivo experiments in nude mice verified that Cu-1 could exert anti-tumor effects through the synergistic action of multiple pathways. In summary, Cu-1 and Ni-1 possess multiple functions including anti-tumor angiogenesis, anti-inflammatory, apoptosis, and copper-induced death, providing theoretical reference for the development of breast cancer drugs.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2358 - 2384"},"PeriodicalIF":8.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726872","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}

{"title":"Manipulating the PANoptosome: baseless hype or a newfound hope for human immunity?","authors":"Dhruv Enuganti,&nbsp;Navya Bandharam,&nbsp;Bhavishya Narra,&nbsp;Vinod Kumar Yata,&nbsp;Narasaiah Kolliputi","doi":"10.1007/s10495-025-02152-7","DOIUrl":"10.1007/s10495-025-02152-7","url":null,"abstract":"<div><p>The human immune system uses many tactics to protect itself from harm, attempting to restore homeostatic conditions. Of these tactics, the primary defense mechanism which is activated is innate immunity. Innate immunity employs phagocytic cells which contain Pattern Recognition Receptors (PRRs) on their surface to promote attachment to certain molecules on pathogens and/or generally damaged/injured cells, which contain Pattern-Associated Molecular Patterns (PAMPs) and Damage/Danger-Associated Molecular Patterns (DAMPs), respectively. DAMPs and PAMPs associate with PRRs in host cells. The interaction between innate immune cells and pathogenic molecular patterns triggers programmed cell death (PCD) pathways; the three main ones being pyroptosis, apoptosis, and necroptosis. Historically, the three were thought to operate autonomously, with no intersection between any, but emerging research has brought a new concept into the limelight: PANoptosis. PANoptosis is now recognized as a distinct, innate immune-regulated inflammatory cell death pathway orchestrated by the PANoptosome, a multiprotein complex that integrates molecular components from pyroptosis, apoptosis, and necroptosis, yet functions independently of them. This integrated pathway plays a crucial role in eliminating infected or damaged cells and modulating immune responses. PANoptosis must be tightly regulated at all times, as any abnormality may increase the chances of a multitude of chronic, severe, and potentially terminal illnesses. Developing a better understanding of PANoptosis offers a promising set of possibilities within immunology research and medicine. By elucidating the relationship between the PCD pathways and how they come together to form a PANoptosome, better targets for treatment can be isolated and integrated into new innovative treatments for a wide range of ailments. This review addresses the mechanisms surrounding PANoptosis and its possible implications for the future of medicine, carrying the potential to bridge the gap of knowledge that exists surrounding complex immunological illnesses and also identifying new markers and significant factors contributing to a treatment/cure.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2008 - 2018"},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697480","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}