Pub Date : 2025-11-01Epub Date: 2025-10-29DOI: 10.1016/S1016-8478(25)00116-5
{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(25)00116-5","DOIUrl":"10.1016/S1016-8478(25)00116-5","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100292"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417356","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}
Pub Date : 2025-11-01Epub Date: 2025-09-10DOI: 10.1016/j.mocell.2025.100276
Thu-Hang Thi Nghiem , Fedho Kusuma , Jeongmin Park , Yeonsoo Joe , Hun Taeg Chung , Jaeseok Han
Ferroptosis is an iron-dependent, lipid-peroxidation-driven form of regulated cell death that is distinct from apoptosis and necroptosis. Its involvement in various diseases highlights the need for reliable detection strategies. We provide a concise guide for ferroptosis detection, outlining key mechanisms, including iron metabolism, lipid remodeling, and antioxidant failure. Cellular, biochemical, genetic, and morphological methods, including viability assays, lipid reactive oxygen species probes, and electron microscopy, have been used to identify ferroptosis in vitro and in vivo. A multiparametric approach is emphasized to ensure the specificity and reproducibility.
{"title":"Brief guide to detecting ferroptosis","authors":"Thu-Hang Thi Nghiem , Fedho Kusuma , Jeongmin Park , Yeonsoo Joe , Hun Taeg Chung , Jaeseok Han","doi":"10.1016/j.mocell.2025.100276","DOIUrl":"10.1016/j.mocell.2025.100276","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent, lipid-peroxidation-driven form of regulated cell death that is distinct from apoptosis and necroptosis. Its involvement in various diseases highlights the need for reliable detection strategies. We provide a concise guide for ferroptosis detection, outlining key mechanisms, including iron metabolism, lipid remodeling, and antioxidant failure. Cellular, biochemical, genetic, and morphological methods, including viability assays, lipid reactive oxygen species probes, and electron microscopy, have been used to identify ferroptosis in vitro and in vivo. A multiparametric approach is emphasized to ensure the specificity and reproducibility.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100276"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054363","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}
Pub Date : 2025-11-01Epub Date: 2025-10-03DOI: 10.1016/j.mocell.2025.100284
Lesly Puspita , Magdalena Deline , Jae-won Shim
Dual SMAD inhibition is a robust and widely adopted protocol for directing human pluripotent stem cells (hPSCs) toward neuronal lineages by blocking transforming growth factor–beta and bone morphogenetic protein pathways. Suppressing transforming growth factor–beta and bone morphogenetic protein signaling enables efficient and reproducible induction of neuroectoderm, serving as the foundation for generating diverse brain region–specific neuronal subtypes. This review outlines the mechanistic basis and major achievements of the dual SMAD inhibition strategy, including its application in 2 recent clinical trials for Parkinson’s disease, and its role in preclinical studies targeting conditions, such as spinal cord injury (SCI), retinal degeneration, and amyotrophic lateral sclerosis (ALS). In addition to its significant contribution to the generation of transplantation-ready grafts from hPSCs, the protocol serves as a valuable platform for disease modeling across various neurological and metabolic disorders. The key strengths include high efficiency, technical simplicity that enables precise control of cell fate using small molecules, versatility in both 2- and 3-dimensional culture systems, and reproducibility across various hPSC lines. This review also addresses key limitations, such as restricted gliogenic capacity and limited neural progenitor cell expansion. Future research should focus on incorporating emerging technologies to advance stem cell–based applications. Overall, dual SMAD inhibition represents a powerful and versatile platform for stem cell–based neuroscience and regenerative medicine.
{"title":"Dual SMAD inhibition as a versatile platform in human pluripotent stem cell–based regenerative medicine and disease modeling","authors":"Lesly Puspita , Magdalena Deline , Jae-won Shim","doi":"10.1016/j.mocell.2025.100284","DOIUrl":"10.1016/j.mocell.2025.100284","url":null,"abstract":"<div><div>Dual SMAD inhibition is a robust and widely adopted protocol for directing human pluripotent stem cells (hPSCs) toward neuronal lineages by blocking transforming growth factor–beta and bone morphogenetic protein pathways. Suppressing transforming growth factor–beta and bone morphogenetic protein signaling enables efficient and reproducible induction of neuroectoderm, serving as the foundation for generating diverse brain region–specific neuronal subtypes. This review outlines the mechanistic basis and major achievements of the dual SMAD inhibition strategy, including its application in 2 recent clinical trials for Parkinson’s disease, and its role in preclinical studies targeting conditions, such as spinal cord injury (SCI), retinal degeneration, and amyotrophic lateral sclerosis (ALS). In addition to its significant contribution to the generation of transplantation-ready grafts from hPSCs, the protocol serves as a valuable platform for disease modeling across various neurological and metabolic disorders. The key strengths include high efficiency, technical simplicity that enables precise control of cell fate using small molecules, versatility in both 2- and 3-dimensional culture systems, and reproducibility across various hPSC lines. This review also addresses key limitations, such as restricted gliogenic capacity and limited neural progenitor cell expansion. Future research should focus on incorporating emerging technologies to advance stem cell–based applications. Overall, dual SMAD inhibition represents a powerful and versatile platform for stem cell–based neuroscience and regenerative medicine.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100284"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233081","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}
Pub Date : 2025-11-01Epub Date: 2025-08-29DOI: 10.1016/j.mocell.2025.100271
Gahbien Lee , Jiyeon Lee , Greg S.B. Suh , Yangkyun Oh
Systemic nutrient sensing is a fundamental process that aligns nutrient availability with an organism’s metabolic demands. This mini-review explores nutrient sensors in the intestine, pancreas, portal vein, and the brain—organs that detect and convey nutrient status to other tissues via neuronal and hormonal signaling. Unlike oral taste receptors that sense external nutrient inputs, these nutrient sensors monitor post ingestive levels of macronutrients (carbohydrates, proteins, and lipids) and micronutrients (vitamins and essential trace elements such as calcium, magnesium, and zinc) within the body. We describe the specific mechanisms by which each organ discerns fluctuations in nutrient concentration and discuss how these signals integrate into endocrine and neural circuits to maintain whole-body nutrient balance. Finally, by comparing mammalian and invertebrate models such as Drosophila, we offer a comprehensive perspective on how organ-level nutrient sensing upholds metabolic homeostasis across diverse species.
{"title":"Post ingestive systemic nutrient sensing for whole-body homeostasis","authors":"Gahbien Lee , Jiyeon Lee , Greg S.B. Suh , Yangkyun Oh","doi":"10.1016/j.mocell.2025.100271","DOIUrl":"10.1016/j.mocell.2025.100271","url":null,"abstract":"<div><div>Systemic nutrient sensing is a fundamental process that aligns nutrient availability with an organism’s metabolic demands. This mini-review explores nutrient sensors in the intestine, pancreas, portal vein, and the brain—organs that detect and convey nutrient status to other tissues via neuronal and hormonal signaling. Unlike oral taste receptors that sense external nutrient inputs, these nutrient sensors monitor post ingestive levels of macronutrients (carbohydrates, proteins, and lipids) and micronutrients (vitamins and essential trace elements such as calcium, magnesium, and zinc) within the body. We describe the specific mechanisms by which each organ discerns fluctuations in nutrient concentration and discuss how these signals integrate into endocrine and neural circuits to maintain whole-body nutrient balance. Finally, by comparing mammalian and invertebrate models such as <em>Drosophila</em>, we offer a comprehensive perspective on how organ-level nutrient sensing upholds metabolic homeostasis across diverse species.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100271"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961765","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}
Pub Date : 2025-11-01Epub Date: 2025-09-04DOI: 10.1016/j.mocell.2025.100274
Tae Young Kim , Byoung Dae Lee
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of misfolded α-synuclein. Current treatments, including dopaminergic medications and deep brain stimulation, provide symptomatic relief but do not halt disease progression. Recent advances in molecular research have enabled the development of disease-modifying strategies targeting key pathogenic mechanisms, such as α-synuclein aggregation, mitochondrial dysfunction, and genetic mutations, including LRRK2 and GBA1. In parallel, pluripotent stem cell-derived dopaminergic neurons have emerged as a scalable and ethically viable source for cell replacement therapy. Early-phase clinical trials have demonstrated the safety and functional integration of these grafts. Ongoing research is now focused on enhancing graft purity, immune compatibility, and anatomical precision, including homotopic transplantation and circuit-level reconstruction. Together, these emerging strategies offer the potential to shift PD treatment paradigms by combining symptomatic control with long-term neural restoration. This review summarizes current therapeutic approaches and highlights recent advances in disease-modifying and regenerative interventions for PD.
{"title":"Current therapeutic strategies in Parkinson’s disease: Future perspectives","authors":"Tae Young Kim , Byoung Dae Lee","doi":"10.1016/j.mocell.2025.100274","DOIUrl":"10.1016/j.mocell.2025.100274","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of misfolded α-synuclein. Current treatments, including dopaminergic medications and deep brain stimulation, provide symptomatic relief but do not halt disease progression. Recent advances in molecular research have enabled the development of disease-modifying strategies targeting key pathogenic mechanisms, such as α-synuclein aggregation, mitochondrial dysfunction, and genetic mutations, including <em>LRRK2</em> and <em>GBA1</em>. In parallel, pluripotent stem cell-derived dopaminergic neurons have emerged as a scalable and ethically viable source for cell replacement therapy. Early-phase clinical trials have demonstrated the safety and functional integration of these grafts. Ongoing research is now focused on enhancing graft purity, immune compatibility, and anatomical precision, including homotopic transplantation and circuit-level reconstruction. Together, these emerging strategies offer the potential to shift PD treatment paradigms by combining symptomatic control with long-term neural restoration. This review summarizes current therapeutic approaches and highlights recent advances in disease-modifying and regenerative interventions for PD.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100274"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008334","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}
Pub Date : 2025-10-01Epub Date: 2025-09-01DOI: 10.1016/j.mocell.2025.100273
Hyunjin Koo , Minah Jung , Sangwoo Lee , Sangjin Go , Yong-Min Kim
Plant synthetic biology is an emerging field that combines bioinformatics, computational gene circuit design, and plant science. It has the potential to be applied in various areas, including the production of pharmaceuticals, vaccines, biofuels, and various biomaterials, including plant natural products. This review highlights recent advancements in plant synthetic biology, particularly in the development and application of biological parts such as promoters and terminators, which play a crucial role in precise gene expression regulation. Furthermore, this review clarified the identification and utilization of bidirectional promoters, which are essential for gene pyramiding, and the significance of maintaining a balance between promoter and terminator combinations for the stability of transgene expression. Furthermore, large-scale identification of promoters using Assay for Transposase-Accessible Chromatin using sequencing and Self-Transcribing Active Regulatory Region sequencing, as well as deep-learning-based models for predicting promoter regions and their transcriptional activity, are discussed. This review provides insights into the identification and application of bioparts in plant synthetic biology to achieve efficient and precise gene regulation.
{"title":"Identification and application of bioparts for plant synthetic biology","authors":"Hyunjin Koo , Minah Jung , Sangwoo Lee , Sangjin Go , Yong-Min Kim","doi":"10.1016/j.mocell.2025.100273","DOIUrl":"10.1016/j.mocell.2025.100273","url":null,"abstract":"<div><div>Plant synthetic biology is an emerging field that combines bioinformatics, computational gene circuit design, and plant science. It has the potential to be applied in various areas, including the production of pharmaceuticals, vaccines, biofuels, and various biomaterials, including plant natural products. This review highlights recent advancements in plant synthetic biology, particularly in the development and application of biological parts such as promoters and terminators, which play a crucial role in precise gene expression regulation. Furthermore, this review clarified the identification and utilization of bidirectional promoters, which are essential for gene pyramiding, and the significance of maintaining a balance between promoter and terminator combinations for the stability of transgene expression. Furthermore, large-scale identification of promoters using Assay for Transposase-Accessible Chromatin using sequencing and Self-Transcribing Active Regulatory Region sequencing, as well as deep-learning-based models for predicting promoter regions and their transcriptional activity, are discussed. This review provides insights into the identification and application of bioparts in plant synthetic biology to achieve efficient and precise gene regulation.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100273"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993005","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}
Pub Date : 2025-10-01Epub Date: 2025-08-14DOI: 10.1016/j.mocell.2025.100265
Jee Yoon Bang , Yongjin Yoo
Microglial biology in Alzheimer’s disease (AD) has become a major focus of investigation, aiming to define how these cells contribute to neurodegeneration and to develop new therapeutic strategies. Once regarded as passive responders, microglia are now recognized as active regulators of brain homeostasis, immune signaling, and synaptic remodeling. Their interactions with genetic risk variants and age-related changes are increasingly understood to play central roles in AD pathogenesis. In this mini-review, we summarize recent progress in identifying microglial contributions to AD through genetic and transcriptomic studies. We discuss how microglia respond to amyloid-β and tau pathology by shifting into diverse functional disease-associated states, which may either protect or harm the brain depending on context and disease stage. We also outline the rationale for targeting microglia through replacement strategies and review emerging approaches using circulation-derived myeloid cells (CDMCs), and human pluripotent stem cell–derived microglia-like cells. These replacement methods have shown potential to rectify microglial functions and modify AD-related pathology in preclinical models, offering a novel therapeutic direction for neurodegenerative diseases.
{"title":"Rationale and emerging evidence for microglial replacement in Alzheimer’s disease","authors":"Jee Yoon Bang , Yongjin Yoo","doi":"10.1016/j.mocell.2025.100265","DOIUrl":"10.1016/j.mocell.2025.100265","url":null,"abstract":"<div><div>Microglial biology in Alzheimer’s disease (AD) has become a major focus of investigation, aiming to define how these cells contribute to neurodegeneration and to develop new therapeutic strategies. Once regarded as passive responders, microglia are now recognized as active regulators of brain homeostasis, immune signaling, and synaptic remodeling. Their interactions with genetic risk variants and age-related changes are increasingly understood to play central roles in AD pathogenesis. In this mini-review, we summarize recent progress in identifying microglial contributions to AD through genetic and transcriptomic studies. We discuss how microglia respond to amyloid-β and tau pathology by shifting into diverse functional disease-associated states, which may either protect or harm the brain depending on context and disease stage. We also outline the rationale for targeting microglia through replacement strategies and review emerging approaches using circulation-derived myeloid cells (CDMCs), and human pluripotent stem cell–derived microglia-like cells. These replacement methods have shown potential to rectify microglial functions and modify AD-related pathology in preclinical models, offering a novel therapeutic direction for neurodegenerative diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100265"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862338","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}
Pub Date : 2025-10-01Epub Date: 2025-08-05DOI: 10.1016/j.mocell.2025.100263
Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim
While tumor-restraining cancer-associated fibroblasts (Tr-CAFs) have been investigated in various cancers, their existence in colorectal cancer remains unexplored. We performed a comprehensive analysis of diverse colorectal cancer datasets, including single-cell RNA-seq/ATAC-seq data from colorectal samples, TCGA RNA-seq, and histological samples. We identified a fibroblast subpopulation uniquely expressing ADAMDEC1, CXCL14, EDNRB, and PROCR, strongly associated with favorable patient outcomes, implicating their role as Tr-CAFs. Pseudotime trajectory analysis suggested these cells as terminally differentiated mucosal fibroblasts. Pathway analysis indicated that this subpopulation was significantly associated with tumor-suppressive functions, such as reduced extracellular matrix secretion, augmented immune response, and enhanced responsiveness to immunotherapy. Single-cell ATAC-seq analysis revealed that this putative Tr-CAF subset exhibited unique epigenetic profiles characterized by superenhancer-regulated tumor-suppressive genes, thereby supporting its identity as a stable lineage rather than a transient phenotypic state induced by external stimuli. Immunohistochemistry showed that key markers identifying this putative Tr-CAF subset—CXCL14, ADAMDEC1, EDNRB, and PROCR—were predominantly localized to fibroblasts within normal colonic mucosa and less frequently in cancer-associated fibroblasts (CAFs). Their expression levels exhibited statistically significant associations with favorable clinicopathological indicators, including prolonged disease-free survival. Notably, ADAMDEC1 expression in CAFs was significantly correlated with T-cell infiltration within the tumor microenvironment. In conclusion, our investigation elucidates the characteristics and clinical relevance of Tr-CAFs in colorectal cancer, suggesting novel avenues for targeted anti-CAF therapy.
{"title":"Identification of a unique subpopulation of mucosal fibroblasts in colorectal cancer with tumor-restraining characteristics","authors":"Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim","doi":"10.1016/j.mocell.2025.100263","DOIUrl":"10.1016/j.mocell.2025.100263","url":null,"abstract":"<div><div>While tumor-restraining cancer-associated fibroblasts (Tr-CAFs) have been investigated in various cancers, their existence in colorectal cancer remains unexplored. We performed a comprehensive analysis of diverse colorectal cancer datasets, including single-cell RNA-seq/ATAC-seq data from colorectal samples, TCGA RNA-seq, and histological samples. We identified a fibroblast subpopulation uniquely expressing ADAMDEC1, CXCL14, EDNRB, and PROCR, strongly associated with favorable patient outcomes, implicating their role as Tr-CAFs. Pseudotime trajectory analysis suggested these cells as terminally differentiated mucosal fibroblasts. Pathway analysis indicated that this subpopulation was significantly associated with tumor-suppressive functions, such as reduced extracellular matrix secretion, augmented immune response, and enhanced responsiveness to immunotherapy. Single-cell ATAC-seq analysis revealed that this putative Tr-CAF subset exhibited unique epigenetic profiles characterized by superenhancer-regulated tumor-suppressive genes, thereby supporting its identity as a stable lineage rather than a transient phenotypic state induced by external stimuli. Immunohistochemistry showed that key markers identifying this putative Tr-CAF subset—CXCL14, ADAMDEC1, EDNRB, and PROCR—were predominantly localized to fibroblasts within normal colonic mucosa and less frequently in cancer-associated fibroblasts (CAFs). Their expression levels exhibited statistically significant associations with favorable clinicopathological indicators, including prolonged disease-free survival. Notably, ADAMDEC1 expression in CAFs was significantly correlated with T-cell infiltration within the tumor microenvironment. In conclusion, our investigation elucidates the characteristics and clinical relevance of Tr-CAFs in colorectal cancer, suggesting novel avenues for targeted anti-CAF therapy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100263"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784856","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}
Pub Date : 2025-10-01Epub Date: 2025-08-06DOI: 10.1016/j.mocell.2025.100264
Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang
Ferroptosis is an iron-dependent and regulated form of cell death, characterized by lipid peroxidation and oxidative stress. The progressive development of pulmonary fibrosis (PF) is closely linked to the ferroptosis pathway. Although the underlying mechanisms remain incompletely defined, this field has drawn intense research attention. Notable progress has been made in identifying ferroptosis-related metabolic pathways and key targets during PF development. In this review, we first summarize the basic regulation of iron metabolism in the human lung, iron metabolic imbalance, and the activation of ferroptosis. Second, we focus on elaborating the mechanistic connections between ferroptosis and PF, encompassing the clinical features, pathological manifestations, and core pathogenic mechanisms of PF, as well as the interplay between ferroptosis and 3 specific cell types in PF: alveolar epithelial cells, macrophages, and fibroblasts. Third, the research progress in the pharmacotherapy of PF is categorized into 3 categories: drugs already approved for PF and those under clinical trials; ferroptosis-targeted therapeutic strategies, including inhibitors, natural compounds, gene therapy, and combination strategies. This review, grounded in key metabolic pathways and therapeutic targets, systematically explores the complex relationships among iron metabolic disorders, ferroptosis, and PF progression. Our aim is to provide a theoretical and practical foundation for ferroptosis-targeted PF treatment.
{"title":"Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy","authors":"Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang","doi":"10.1016/j.mocell.2025.100264","DOIUrl":"10.1016/j.mocell.2025.100264","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent and regulated form of cell death, characterized by lipid peroxidation and oxidative stress. The progressive development of pulmonary fibrosis (PF) is closely linked to the ferroptosis pathway. Although the underlying mechanisms remain incompletely defined, this field has drawn intense research attention. Notable progress has been made in identifying ferroptosis-related metabolic pathways and key targets during PF development. In this review, we first summarize the basic regulation of iron metabolism in the human lung, iron metabolic imbalance, and the activation of ferroptosis. Second, we focus on elaborating the mechanistic connections between ferroptosis and PF, encompassing the clinical features, pathological manifestations, and core pathogenic mechanisms of PF, as well as the interplay between ferroptosis and 3 specific cell types in PF: alveolar epithelial cells, macrophages, and fibroblasts. Third, the research progress in the pharmacotherapy of PF is categorized into 3 categories: drugs already approved for PF and those under clinical trials; ferroptosis-targeted therapeutic strategies, including inhibitors, natural compounds, gene therapy, and combination strategies. This review, grounded in key metabolic pathways and therapeutic targets, systematically explores the complex relationships among iron metabolic disorders, ferroptosis, and PF progression. Our aim is to provide a theoretical and practical foundation for ferroptosis-targeted PF treatment.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100264"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804373","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}
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