IF 10.7

MedComm Pub Date : 2024-10-23 DOI: 10.1002/mco2.787

Xi Chen, Yixiao Yuan, Fan Zhou, Lihua Li, Jun Pu, Xiulin Jiang

{"title":"RNA modification in normal hematopoiesis and hematologic malignancies","authors":"Xi Chen, Yixiao Yuan, Fan Zhou, Lihua Li, Jun Pu, Xiulin Jiang","doi":"10.1002/mco2.787","DOIUrl":"10.1002/mco2.787","url":null,"abstract":"N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotic cells. Previous studies have shown that m6A plays a critical role under both normal physiological and pathological conditions. Hematopoiesis and differentiation are highly regulated processes, and recent studies on m6A mRNA methylation have revealed how this modification controls cell fate in both normal and malignant hematopoietic states. However, despite these insights, a comprehensive understanding of its complex roles between normal hematopoietic development and malignant hematopoietic diseases remains elusive. This review first provides an overview of the components and biological functions of m6A modification regulators. Additionally, it highlights the origin, differentiation process, biological characteristics, and regulatory mechanisms of hematopoietic stem cells, as well as the features, immune properties, and self-renewal pathways of leukemia stem cells. Last, the article systematically reviews the latest research advancements on the roles and mechanisms of m6A regulatory factors in normal hematopoiesis and related malignant diseases. More importantly, this review explores how targeting m6A regulators and various signaling pathways could effectively intervene in the development of leukemia, providing new insights and potential therapeutic targets. Targeting m6A modification may hold promise for achieving more precise and effective leukemia treatments.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Feedback loop LINC00511–YTHDF2–SOX2 regulatory network drives cholangiocarcinoma progression and stemness LINC00511-YTHDF2-SOX2反馈回路调控网络驱动胆管癌的进展和干性。

IF 10.7

MedComm Pub Date : 2024-10-22 DOI: 10.1002/mco2.743

Canghai Guan, Xinlei Zou, Xin Gao, Sidi Liu, Jianjun Gao, Wujiang Shi, Qingfu Dong, Xingming Jiang, Xiangyu Zhong

{"title":"Feedback loop LINC00511–YTHDF2–SOX2 regulatory network drives cholangiocarcinoma progression and stemness","authors":"Canghai Guan, Xinlei Zou, Xin Gao, Sidi Liu, Jianjun Gao, Wujiang Shi, Qingfu Dong, Xingming Jiang, Xiangyu Zhong","doi":"10.1002/mco2.743","DOIUrl":"10.1002/mco2.743","url":null,"abstract":"Cholangiocarcinoma (CCA) was identified as a malignant tumor with rising incidence and mortality rates, and the roles of long noncoding RNA (lncRNA) in CCA remained not entirely clear. In this study, LINC00511 had high expression in CCA, which was closely related to poor prognosis. Knockdown of LINC00511 significantly inhibited cell malignant biological behaviors. It also affected the stemness of CCA, evidenced by decreased SOX2 protein expression. Moreover, the study revealed the interaction of LINC00511, YTHDF2, and SOX2 in CCA. Specifically, LINC00511 facilitated the formation of a complex with YTHDF2 on SOX2 mRNA, which uniquely enhances the mRNA's stability through m6A methylation sites. This stabilization appears crucial for maintaining malignant behaviors in CCA cells. Additionally, LINC00511 modulated SOX2 expression via the PI3K/AKT signaling pathway. Meanwhile, SOX2 can also promote LINC00511 expression as an upstream transcription factor, thereby confirming a positive feedback loop formed by LINC00511, YTHDF2, and SOX2, which plays a significant role in the occurrence and development of CCA. Finally, the study successfully constructed two patient-derived xenograft models, revealing the vital role of LINC00511 in CCA development. In summary, this research provides a comprehensive understanding of the role of LINC00511 in the pathogenesis of CCA.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights into the mechanotransducing mechanism of FtsEX in cell division 从结构上揭示 FtsEX 在细胞分裂中的机械传动机制。

IF 10.7

MedComm Pub Date : 2024-10-20 DOI: 10.1002/mco2.688

Yuejia Chen, Du Guo, Xin Wang, Changbin Zhang, Yatian Chen, Qinghua Luo, Yujiao Chen, Lili Yang, Zhibo Zhang, Tian Hong, Zhengyu Zhang, Haohao Dong, Shenghai Chang, Jianping Hu, Xiaodi Tang

{"title":"Structural insights into the mechanotransducing mechanism of FtsEX in cell division","authors":"Yuejia Chen, Du Guo, Xin Wang, Changbin Zhang, Yatian Chen, Qinghua Luo, Yujiao Chen, Lili Yang, Zhibo Zhang, Tian Hong, Zhengyu Zhang, Haohao Dong, Shenghai Chang, Jianping Hu, Xiaodi Tang","doi":"10.1002/mco2.688","DOIUrl":"10.1002/mco2.688","url":null,"abstract":"The filamentous temperature-sensitive (Fts) protein FtsEX plays a pivotal role in Escherichia coli (E. coli) cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP-binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive. Due to the inherent instability of this type of ABC transporter protein in vitro, the conformation of FtsEX has solely been determined in the stabilized ATP-bound state. To elucidate the dynamics of FtsEX, we characterized FtsEX and EnvC of various functional structures through cryo-electron microscopy (cryo-EM) and homology modeling. We validated the structures by molecular dynamics simulations. By site-directed mutagenesis and phenotype screening, we also identified the functional residues involved in allosteric communication between FtsE and FtsX as well as FtsX and EnvC. Additionally, we discovered a potential role of phospholipids in stabilizing the complex conformation during mechanotransmission. This comprehensive exploration significantly enhances our understanding of the intricate mechanisms governing bacterial cell division and unveils potential molecular targets for developing innovative antimicrobial drugs to combat antibiotic resistance.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Progressive cancer targeting by programmable aptamer-tethered nanostructures 通过可编程适配体系留纳米结构实现渐进式癌症靶向。

IF 10.7

MedComm Pub Date : 2024-10-20 DOI: 10.1002/mco2.775

Fatemeh Mohammadi, Hamed Zahraee, Farkhonde Zibadi, Zahra Khoshbin, Mohammad Ramezani, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi

{"title":"Progressive cancer targeting by programmable aptamer-tethered nanostructures","authors":"Fatemeh Mohammadi, Hamed Zahraee, Farkhonde Zibadi, Zahra Khoshbin, Mohammad Ramezani, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi","doi":"10.1002/mco2.775","DOIUrl":"10.1002/mco2.775","url":null,"abstract":"Scientific research in recent decades has affirmed an increase in cancer incidence as a cause of death globally. Cancer can be considered a plurality of various diseases rather than a single disease, which can be a multifaceted problem. Hence, cancer therapy techniques acquired more accelerated and urgent approvals compared to other therapeutic approaches. Radiotherapy, chemotherapy, immunotherapy, and surgery have been widely adopted as routine cancer treatment strategies to suppress disease progression and metastasis. These therapeutic approaches have lengthened the longevity of countless cancer patients. Nonetheless, some inherent limitations have restricted their application, including insignificant therapeutic efficacy, toxicity, negligible targeting, non-specific distribution, and multidrug resistance. The development of therapeutic oligomer nanoconstructs with the advantages of chemical solid-phase synthesis, programmable design, and precise adjustment is crucial for advancing smart targeted drug nanocarriers. This review focuses on the significance of the different aptamer-assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery. We discuss recent advancements in the design and utilization of aptamer-tethered nanostructures to enhance the efficacy of cancer treatment. Valuably, this comprehensive review highlights self-assembled aptamers as the exceptionally intelligent nano-biomaterials for targeted drug delivery based on their superior stability, high specificity, excellent recoverability, inherent biocompatibility, and versatile functions.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanomedicine for cancer patient-centered care 以癌症患者为中心的纳米医学护理。

IF 10.7

MedComm Pub Date : 2024-10-20 DOI: 10.1002/mco2.767

Carlo Sorrentino, Stefania Livia Ciummo, Cristiano Fieni, Emma Di Carlo

{"title":"Nanomedicine for cancer patient-centered care","authors":"Carlo Sorrentino, Stefania Livia Ciummo, Cristiano Fieni, Emma Di Carlo","doi":"10.1002/mco2.767","DOIUrl":"10.1002/mco2.767","url":null,"abstract":"Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low-toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine-based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Several nanoformulations are currently in clinical trials, and some have been approved and marketed. However, their large-scale production and use are still hindered by an in-depth debate involving ethics, intellectual property, safety and health concerns, technical issues, and costs. Here, we survey the key approaches, with specific reference to organ-on chip technology, and cutting-edge tools, such as CRISPR/Cas9 genome editing, through which nanosystems can meet the needs for personalized diagnostics and therapy in cancer patients. An update is provided on the nanopharmaceuticals approved and marketed for cancer therapy and those currently undergoing clinical trials. Finally, we discuss the emerging avenues in the field and the challenges to be overcome for the transfer of nano-based precision oncology into clinical daily life.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets 缺氧与衰老：分子机制、疾病和治疗目标

IF 10.7

MedComm Pub Date : 2024-10-15 DOI: 10.1002/mco2.786

Ayesha Nisar, Sawar Khan, Wen Li, Li Hu, Priyadarshani Nadeeshika Samarawickrama, Naheemat Modupeola Gold, Meiting Zi, Sardar Azhar Mehmood, Jiarong Miao, Yonghan He

{"title":"Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets","authors":"Ayesha Nisar, Sawar Khan, Wen Li, Li Hu, Priyadarshani Nadeeshika Samarawickrama, Naheemat Modupeola Gold, Meiting Zi, Sardar Azhar Mehmood, Jiarong Miao, Yonghan He","doi":"10.1002/mco2.786","DOIUrl":"https://doi.org/10.1002/mco2.786","url":null,"abstract":"Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia-inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age-related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia-targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia-induced pathways to enhance healthy aging and reduce the burden of age-related diseases.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inducing disulfidptosis in tumors:potential pathways and significance 诱导肿瘤中的二硫化硫：潜在途径和意义

IF 10.7

MedComm Pub Date : 2024-10-15 DOI: 10.1002/mco2.791

Tao Mi, Xiangpan Kong, Meiling Chen, Peng Guo, Dawei He

{"title":"Inducing disulfidptosis in tumors:potential pathways and significance","authors":"Tao Mi, Xiangpan Kong, Meiling Chen, Peng Guo, Dawei He","doi":"10.1002/mco2.791","DOIUrl":"https://doi.org/10.1002/mco2.791","url":null,"abstract":"Regulated cell death (RCD) is crucial for the elimination of abnormal cells. In recent years, strategies aimed at inducing RCD, particularly apoptosis, have become increasingly important in cancer therapy. However, the ability of tumor cells to evade apoptosis has led to treatment resistance and relapse, prompting extensive research into alternative death processes in cancer cells. A recent study identified a novel form of RCD known as disulfidptosis, which is linked to disulfide stress. Cancer cells import cystine from the extracellular environment via solute carrier family 7 member 11 (SLC7A11) and convert it to cysteine using nicotinamide adenine dinucleotide phosphate (NADPH). When NADPH is deficient or its utilization is impaired, cystine accumulates, leading to the formation of disulfide bonds in the actin cytoskeleton, triggering disulfidptosis. Disulfidptosis reveals a metabolic vulnerability in tumors, offering new insights into cancer therapy strategies. This review provides a detailed overview of the mechanisms underlying disulfidptosis, the current research progress, and limitations. It also highlights innovative strategies for inducing disulfidptosis and explores the potential of combining these approaches with traditional cancer therapies, particularly immunotherapy, to expedite clinical translation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vitamin B12 protects necrosis of acinar cells in pancreatic tissues with acute pancreatitis 维生素 B12 可保护急性胰腺炎胰腺组织中的尖突细胞坏死

IF 10.7

MedComm Pub Date : 2024-10-15 DOI: 10.1002/mco2.686

Yulin Chen, Xue Li, Ran Lu, Yinchun Lv, Yongzi Wu, Junman Ye, Jin Zhao, Li Li, Qiaorong Huang, Wentong Meng, Feiwu Long, Wei Huang, Qing Xia, Jianbo Yu, Chuanwen Fan, Xianming Mo

{"title":"Vitamin B12 protects necrosis of acinar cells in pancreatic tissues with acute pancreatitis","authors":"Yulin Chen, Xue Li, Ran Lu, Yinchun Lv, Yongzi Wu, Junman Ye, Jin Zhao, Li Li, Qiaorong Huang, Wentong Meng, Feiwu Long, Wei Huang, Qing Xia, Jianbo Yu, Chuanwen Fan, Xianming Mo","doi":"10.1002/mco2.686","DOIUrl":"https://doi.org/10.1002/mco2.686","url":null,"abstract":"Pharmacological agents regarding the most optimal treatments of acute pancreatitis remain. One-carbon metabolism nutrients as therapeutic agents in many diseases might be involved in acute pancreatitis. The roles are acquired exploration in acute pancreatitis. We utilized Mendelian randomization to assess the causal impact of folate, homocysteine, and vitamin B12 (VB12) on acute pancreatitis. Wild-type and corresponding genetically modified mouse models were used to verify the genetic correlating findings. A negative association between genetically predicted serum VB12 levels and risks of acute pancreatitis was identified in human population. The transcobalamin receptor (TCblR)/CD320 gene ablation that decreased cellular VB12 uptake and ATP production in pancreatic tissues promoted necrosis, resulting in much severe pathological changes of induced acute pancreatitis in mice. VB12 pretreatment and posttreatment dramatically increased ATP levels in pancreatic tissues and reduced the necrosis, then the elevated levels of amylase in serum, the levels of CK-19, the activity of trypsin, and T lymphocyte infiltration in pancreatic tissues, prevented the pancreatic gross loss and ameliorated histopathological changes of mouse pancreases with induced acute pancreatitis. The results reveal that VB12 is potential as a therapeutic agent to inhibit tissue injuries and adaptive inflammatory responses in the pancreas in patients with acute pancreatitis.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting esophageal carcinoma: molecular mechanisms and clinical studies 食管癌靶向治疗：分子机制与临床研究

IF 10.7

MedComm Pub Date : 2024-10-15 DOI: 10.1002/mco2.782

Wenjing Wang, Lisha Ye, Huihui Li, Weimin Mao, Xiaoling Xu

{"title":"Targeting esophageal carcinoma: molecular mechanisms and clinical studies","authors":"Wenjing Wang, Lisha Ye, Huihui Li, Weimin Mao, Xiaoling Xu","doi":"10.1002/mco2.782","DOIUrl":"https://doi.org/10.1002/mco2.782","url":null,"abstract":"Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody–drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.782","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations in the axon initial segment plasticity is involved in early pathogenesis in Alzheimer's disease 轴突初段可塑性的改变与阿尔茨海默病的早期发病机制有关

IF 10.7

MedComm Pub Date : 2024-10-14 DOI: 10.1002/mco2.768

Yu Li, Han Wang, Yiming Wang, Zhiya Chen, Yiqiong Liu, Wu Tian, Xinrui Kang, Abolghasem Pashang, Don Kulasiri, Xiaoli Yang, Hung Wing Li, Yan Zhang

{"title":"Alterations in the axon initial segment plasticity is involved in early pathogenesis in Alzheimer's disease","authors":"Yu Li, Han Wang, Yiming Wang, Zhiya Chen, Yiqiong Liu, Wu Tian, Xinrui Kang, Abolghasem Pashang, Don Kulasiri, Xiaoli Yang, Hung Wing Li, Yan Zhang","doi":"10.1002/mco2.768","DOIUrl":"https://doi.org/10.1002/mco2.768","url":null,"abstract":"Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the early presence of amyloid-β (Aβ) and hyperphosphorylated tau. Identifying the neuropathological changes preceding cognitive decline is crucial for early intervention. Axon initial segment (AIS) maintains the orderly structure of the axon and is responsible for initiating action potentials (APs). To investigate the role of AIS in early stages of AD pathogenesis, we focused on alterations in the AIS of neurons from APP/PS1 mouse models harboring familial AD mutations. AIS length and electrophysiological properties were assessed in neurons using immunostaining and patch-clamp techniques. The expression and function of ankyrin G (AnkG) isoforms were evaluated by western blot and rescue experiments. We observed a significant shortening of AIS in APP/PS1 mice, which correlated with impaired action potential propagation. Furthermore, a decrease in the 480 kDa isoform of AnkG was observed. Rescue of this isoform restored AIS plasticity and improved long-term potentiation in APP/PS1 neurons. Our study implicates AIS plasticity alterations and AnkG dysregulation as early events in AD. The restoration of AIS integrity by the 480 kDa AnkG isoform presents a potential therapeutic strategy for AD, underscoring the importance of targeting AIS stability in neurodegenerative diseases.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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