Journal of Molecular Cell Biology最新文献_第10页

Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice. 氩改善小胶质细胞介导的海马神经元的高兴奋性以减轻小鼠的焦虑样行为。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf006

Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li

{"title":"Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice.","authors":"Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li","doi":"10.1093/jmcb/mjaf006","DOIUrl":"10.1093/jmcb/mjaf006","url":null,"abstract":"The role of inflammation in psychiatric disorders, such as anxiety, has gained increasing attention, with the hippocampus being identified as a key region involved in emotional regulation. Argon has been reported to alleviate the symptoms of psychiatric disorders; however, its underlying mechanism remains unclear. In this study, we found that argon significantly suppressed lipopolysaccharide-induced anxiety-like behaviors and attenuated hippocampal neuronal hyperexcitability in mice. By analyzing neuronal excitability following microglial depletion and subsequent repopulation, as well as assessing microglial morphology, we confirmed that microglia are key targets of inflammation and validated the inhibitory effects of argon. Electrophysiological studies and transcriptome sequencing revealed that argon inhibited the microglia-released inflammatory cytokines via the Toll-like receptor 4/nuclear factor-κB signaling pathway, thereby improving the excitability of hippocampal neurons. Collectively, this study provides evidence that the regulation of microglia may be the underlying mechanism by which argon ameliorates neuroinflammation-induced anxiety-like behaviors.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12604011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557190","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

Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis. 神经毒物（MPTP和6-羟多巴胺）和α-突触核蛋白诱导帕金森病的致病机制：一个统一的假说。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-10-17 DOI: 10.1093/jmcb/mjaf041

Bao Ting Zhu

{"title":"Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.","authors":"Bao Ting Zhu","doi":"10.1093/jmcb/mjaf041","DOIUrl":"10.1093/jmcb/mjaf041","url":null,"abstract":"The mechanism underlying the selective loss of dopaminergic neurons in Parkinson's disease (PD) is still not understood at present. MPTP, an illicit drug contaminant, can selectively induce parkinsonism in humans and animals which is very similar to idiopathic PD. Like MPTP, 6-hydroxydopamine (6-OHDA) is another neurotoxicant also capable of selectively inducing parkinsonism in animal models. In this paper, a unifying hypothesis is proposed, which offers a plausible explanation for the pathogenic mechanism of parkinsonism induced by MPTP and 6-OHDA. This hypothesis has three core elements. (i) The vesicular monoamine transporter 2 (VMAT2) is the transporter responsible for the reverse transport (efflux) of the misplaced cytosolic dopamine (DA). (ii) Activation of VMAT2-mediated DA reverse transport is caused by elevated oxidative stress, often resulting from the buildup of cytosolic DA in dopaminergic neurons. (iii) VMAT2 is a major target of MPP+ (a toxic metabolite of MPTP) and 6-OHDA, and inhibition of VMAT2-mediated DA reverse transport by MPP+ or 6-OHDA will result in the buildup of cytosolic DA, and its subsequent oxidation/auto-oxidation will further heighten oxidative stress and generate chemically-reactive, neurotoxic DA derivatives. These DA-associated oxidative changes jointly contribute to the selective injury to dopaminergic neurons and the induction of parkinsonism. This mechanistic hypothesis agrees with a large body of experimental observations, and also offers a mechanistic explanation for many experimental findings. Additionally, this hypothesis offers mechanistic insights into the pathogenic role of α-synuclein in human PD based on its strong ability to suppress VMAT2-mediated DA reverse transport in dopaminergic neurons.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549774","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

Combination therapy dramatically promotes remyelination. 联合治疗可显著促进髓鞘再生。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf005

Yawen Li, Pingping Li, Yixuan Song, Wenjun Zhang, Xinyue Jiang, Siyi Chen, Wei Luo, Caiyun Ma, Changqing Liu, Jianguo Niu, Aibin Liang, Yarui Du, Bo O Zhou, Mingliang Zhang

{"title":"Combination therapy dramatically promotes remyelination.","authors":"Yawen Li, Pingping Li, Yixuan Song, Wenjun Zhang, Xinyue Jiang, Siyi Chen, Wei Luo, Caiyun Ma, Changqing Liu, Jianguo Niu, Aibin Liang, Yarui Du, Bo O Zhou, Mingliang Zhang","doi":"10.1093/jmcb/mjaf005","DOIUrl":"10.1093/jmcb/mjaf005","url":null,"abstract":"Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system that is characterized by demyelination, axonal degeneration, and progressive neurological disability and is so far incurable. Current medications are predominantly immune-targeted but fail to prevent disease progression due to their inability to actively promote remyelination. Small molecules have been reported to promote myelin regeneration but their therapeutic efficacy is limited by insufficient immune modulation. Thus, the strategies achieving both immunomodulation and active myelin regeneration are highly desired. Here, we investigated a combination therapy (CT) for MS designed to simultaneously modulate immune responses and promote oligodendrocyte precursor cell differentiation and in situ remyelination in an experimental autoimmune encephalomyelitis mouse model. Remarkably, CT suppressed acute inflammatory activity, activated the signaling pathways for myelin development, induced the expression of myelin-related genes, and significantly promoted remyelination and the recovery of motor performance. Furthermore, a reduced immunomodulator dosage or shorter treatment duration with small-molecule drugs achieved comparable symptom reversal. Our findings demonstrate the potential of CT to address complex pathobiology and lay a foundation for developing novel therapeutic strategies for MS.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557192","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

Akt-elicited phosphorylation of Acapin steers cell migration. akt诱导的Acapin磷酸化引导细胞迁移。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf010

Chunyue Wang, Jiajia Zhou, Tao Li, Shihao Du, Tetsuro Urushidani, Dongmei Wang, Yong Chen, McKay Mullen, Xinwang Cao, Shi-Yuan Cheng, Xia Ding, Fengrui Yang, Xuebiao Yao

{"title":"Akt-elicited phosphorylation of Acapin steers cell migration.","authors":"Chunyue Wang, Jiajia Zhou, Tao Li, Shihao Du, Tetsuro Urushidani, Dongmei Wang, Yong Chen, McKay Mullen, Xinwang Cao, Shi-Yuan Cheng, Xia Ding, Fengrui Yang, Xuebiao Yao","doi":"10.1093/jmcb/mjaf010","DOIUrl":"10.1093/jmcb/mjaf010","url":null,"abstract":"Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia. However, the molecular mechanisms underlying dynamic recruitment of vesicular membrane during cell migration remain elusive. Here, we report a critical mechanism underlying epidermal growth factor (EGF)-elicited Akt signaling-steered cell migration. Using functional proteomics screen, we identified a novel ADP-ribosylation factor 6 (ARF6)-ACAP4 signaling regulator, Acapin, which inhibits the GTPase-activating protein (GAP) activity of ACAP4 to activate ARF6 GTPase in vitro. In cells, EGF stimulation elicits Akt signaling, which recruits Acapin to the lamellipodium membrane via phosphorylation of Acapin at its Ser247 residue and enhances the binding of Acapin to ACAP4 to elevate the ARF6-GTP level. Therefore, Acapin is required for efficiently stimulating cell migration by EGF-Akt signaling. Together, our results demonstrate the role of Acapin in relaying the Akt signaling cascade during cell migration processes.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624979","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

Structural insights into CRL2FEM1C ubiquitin ligase-mediated protein ubiquitination. CRL2FEM1C泛素连接酶介导的蛋白泛素化的结构见解。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf016

Hualin Zhou, Mor Israel-Gueta, Xinyan Chen, Qiong Guo, Xing Liu, Itay Koren, Chao Xu

引用次数: 0

A nomogram to predict gestational diabetes mellitus: a multicenter retrospective study. 预测妊娠期糖尿病的nomogram：一项多中心回顾性研究。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf008

Rui Zhang, Zhangyan Li, Nuerbiya Xilifu, Mengxue Yang, Yongling Dai, Shufei Zang, Jun Liu

{"title":"A nomogram to predict gestational diabetes mellitus: a multicenter retrospective study.","authors":"Rui Zhang, Zhangyan Li, Nuerbiya Xilifu, Mengxue Yang, Yongling Dai, Shufei Zang, Jun Liu","doi":"10.1093/jmcb/mjaf008","DOIUrl":"10.1093/jmcb/mjaf008","url":null,"abstract":"While gestational diabetes mellitus (GDM) poses great threat to the health of mothers and children, there is no standard early prediction model for this disease yet. This study developed and evaluated a nomogram for predicting GDM in early pregnancy. Overall, 1824 pregnant women were randomly divided into the training and internal validation sets in the ratio of 7:3, with additional 1604 pregnant women for external validation. Multivariate logistic regression analysis was used to develop a prediction model for GDM, and a nomogram was utilized for model visualization. Risk factors in the prediction model involved age, pre-pregnancy body mass index, reproductive history, family history of diabetes, creatinine level, triglyceride level, low-density lipoprotein level, neutrophil count, and monocyte count. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision clinical analysis (DCA). The area under ROC curve (AUC) value of the model was 0.804 for the training set, and similar AUC values were obtained for the internal (0.800) and external (0.829) validation sets, verifying the stability of the model. The calibration curves showed that the probabilities of GDM predicted by the nomogram highly correlated with the observed frequency values. The DCA curves indicated that the prediction model is clinically useful, thus potentially aiding early pregnancy management in women.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597239","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

Characterization of the nucleolar localization signal of TRMT10A and its importance for the m1G9 methylation of tRNAs in mammalian cells. 哺乳动物细胞中TRMT10A核仁定位信号的表征及其对trna m1G9甲基化的重要性

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf011

Tianyang Luo, Zhiyuan Shi, Haibin Yang, Jiafan Miao, Zilong Chang, Jie Zou, Qiang Zeng, Wenbin Wu, Yanan Jiang, Xiaoling Xie, Liu Cao, Hong Peng, Chunmei Li, Deyin Guo, Junyu Wu

引用次数: 0

Silencing GGH induces autophagy by increasing folate stress and production of NADH. 沉默GGH通过增加叶酸应激和NADH的产生诱导自噬。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-09-10 DOI: 10.1093/jmcb/mjaf014

Yu Li, Yuhui Du, Sijie Chen, Zhangrong Xie, Xinrui Li, Baoyue Lin, Zhiqing Zhou, Huijie Zhao, Guoan Chen

{"title":"Silencing GGH induces autophagy by increasing folate stress and production of NADH.","authors":"Yu Li, Yuhui Du, Sijie Chen, Zhangrong Xie, Xinrui Li, Baoyue Lin, Zhiqing Zhou, Huijie Zhao, Guoan Chen","doi":"10.1093/jmcb/mjaf014","DOIUrl":"10.1093/jmcb/mjaf014","url":null,"abstract":"There is an inextricable link between metabolic disorders and autophagy. Gamma-glutamyl hydrolase (GGH) is a lysosomal glycoprotein that reduces intracellular folate stress by catalyzing the hydrolysis of polyglutamylated folate into transportable monoglutamate. The relationship between folate metabolism, involving the folate metabolic enzyme GGH, and autophagy has rarely been reported. In this study, we found that GGH functions as a crucial oncogene in lung adenocarcinomas. Importantly, we found that cell autophagy and autophagic cell death are induced by GGH silencing through the elevated folate stress resulting from folate metabolism and the folate metabolite nicotinamide adenine dinucleotide (NADH). By increasing the NADH/NAD+ ratio, silencing GGH activates adenosine monophosphate-activated protein kinase (AMPK) through the activation of LKB1 and CAMKK2, as well as enhanced AMP/ATP and ADP/ATP ratios, which then triggers the initiation of early autophagy, finally resulting in autophagic cell death. Taken together, our study suggests that GGH may not only serve as a prognostic marker but also play a critical role in the initiation of early autophagy. Interventions targeting GGH to regulate folate metabolism and the proportion of NADH/NAD+ may have translational potential for precision therapy in human cancer.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014701","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

Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage. Wnt/β-catenin通路通过akap6介导的RyR2磷酸化和肌浆网钙渗漏诱导心功能障碍。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf002

Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li

{"title":"Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage.","authors":"Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li","doi":"10.1093/jmcb/mjaf002","DOIUrl":"10.1093/jmcb/mjaf002","url":null,"abstract":"The Wnt signaling pathway plays important roles in cardiomyocyte proliferation and cardiac regeneration after heart injury. Abnormal activation of the Wnt pathway causes a reduction in cardiomyocyte function, leading to hypertrophy, fibrosis, and heart failure. However, the mechanism through which Wnt signaling affects cardiomyocyte function during cardiac diseases is still unclear. In this study, we observed that activation of the Wnt/β-catenin pathway, but not the Wnt/Ca2+ pathway, leads to significant cytosol calcium enrichment. Such an effect can be inhibited by cycloheximide that blocks the downstream gene expression. By analyzing the transcriptome data, we found that activation of the Wnt/β-catenin pathway significantly upregulates the expression level of muscle-selective A kinase anchoring protein (mAKAP, also called AKAP6), a scaffold protein that can improve the interaction between protein kinase A (PKA) and its substrate ryanodine receptor 2 (RyR2) in cardiomyocytes. We further identified that AKAP6 is a target gene of the canonical Wnt pathway and increasing AKAP6 expression can enhance RyR2 phosphorylation by PKA, causing the sarcoplasmic reticulum calcium leakage and finally heart dysfunction. Our finding that the Wnt/β-catenin pathway affects cardiac calcium regulation via AKAP6 and RyR2 provides profound insights into heart diseases and sheds light on potential therapeutic strategies.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649326","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

Comments on 'Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages'. “巨噬细胞对细胞外基质的降解是由维门蛋白中间丝协调肌动蛋白应激纤维和足小体决定的”。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf004

Sandrine Etienne-Manneville

引用次数: 0