Journal of Molecular Medicine-Jmm最新文献

{"title":"Role and molecular mechanism of NOD2 in chronic non-communicable diseases.","authors":"Lingjun Kong, Yanhua Cao, Yanan He, Yahui Zhang","doi":"10.1007/s00109-024-02451-7","DOIUrl":"10.1007/s00109-024-02451-7","url":null,"abstract":"<p><p>Nucleotide-binding oligomerization domain containing 2 (NOD2), located in the cell cytoplasm, is a pattern recognition receptor belonging to the innate immune receptor family. It mediates the innate immune response by identifying conserved sequences in bacterial peptide glycans and plays an essential role in maintaining immune system homeostasis. Gene mutations of NOD2 lead to the development of autoimmune diseases such as Crohn's disease and Blau syndrome. Recently, NOD2 has been shown to be associated with the pathogenesis of diabetes, cardiac-cerebral diseases, and cancers. However, the function of NOD2 in these non-communicable diseases (CNCDs) is not well summarized in reviews. Our report mainly discusses the primary function and molecular mechanism of NOD2 as well as its potential clinical significance in CNCDs.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria targeted esculetin administration improves insulin resistance and hyperglycemia-induced atherosclerosis in db/db mice.","authors":"Gajalakshmi Singuru, Sriravali Pulipaka, Altab Shaikh, Shashikanta Sahoo, Aruna Jangam, Rajamannar Thennati, Srigiridhar Kotamraju","doi":"10.1007/s00109-024-02449-1","DOIUrl":"https://doi.org/10.1007/s00109-024-02449-1","url":null,"abstract":"<p><p>The development and progression of hyperglycemia (HG) and HG-associated atherosclerosis are exacerbated by mitochondrial dysfunction due to dysregulated mitochondria-derived ROS generation. We recently synthesized a novel mitochondria-targeted esculetin (Mito-Esc) and tested its dose-response therapeutic efficacy in mitigating HG-induced atherosclerosis in db/db mice. In comparison to simvastatin and pioglitazone, Mito-Esc administration resulted in a considerable reduction in body weights and improved glucose homeostasis, possibly by reducing hepatic gluconeogenesis, as indicated by a reduction in glycogen content, non-esterified free fatty acids (NEFA) levels, and fructose 1,6-bisphosphatase (FBPase) activity. Interestingly, Mito-Esc treatment, by regulating phospho-IRS and phospho-AKT levels, greatly improved palmitate-induced insulin resistance, resulting in enhanced glucose uptake in adipocytes and HepG2 cells. Also, and importantly, Mito-Esc administration prevented HG-induced atheromatous plaque formation and lipid accumulation in the descending aorta. In addition, Mito-Esc administration inhibited the HG-mediated increase in VACM, ICAM, and MAC3 levels in the aortic tissue, as well as reduced the serum pro-inflammatory cytokines and markers of senescence. In line with this, Mito-Esc significantly inhibited monocyte adherence to human aortic endothelial cells (HAECs) treated with high glucose and reduced high glucose-induced premature senescence in HAECs by activating the AMPK-SIRT1 pathway. In contrast, Mito-Esc failed to regulate high glucose-induced endothelial cell senescence under AMPK/SIRT1-depleted conditions. Together, the therapeutic efficacy of Mito-Esc in the mitigation of hyperglycemia-induced insulin resistance and the associated atherosclerosis is in part mediated by potentiating the AMPK-SIRT1 axis. KEY MESSAGES: Mito-Esc administration significantly mitigates diabetes-induced atherosclerosis. Mito-Esc improves hyperglycemia (HG)-associated insulin resistance. Mito-Esc inhibits HG-induced vascular senescence and inflammation in the aorta. Mito-Esc-mediated activation of the AMPK-SIRT1 axis regulates HG-induced endothelial cell senescence.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of aryl hydrocarbon receptor restricts omeprazole-induced chronic kidney disease.","authors":"Nan Sun, Yimeng Zhang, Lin Ding, Xin An, Fang Bai, Yanjiang Yang, Kuipeng Yu, Jiahui Fan, Lei Liu, Huimin Yang, Xiangdong Yang","doi":"10.1007/s00109-024-02429-5","DOIUrl":"10.1007/s00109-024-02429-5","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage activation contributes to diabetic retinopathy.","authors":"Yi Zhang, Aiyi Zhou","doi":"10.1007/s00109-024-02437-5","DOIUrl":"10.1007/s00109-024-02437-5","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is recognized as a neurovascular complication of diabetes, and emerging evidence underscores the pivotal role of inflammation in its pathophysiology. Macrophage activation is increasingly acknowledged as a key contributor to the onset and progression of DR. Different populations of macrophages originating from distinct sources contribute to DR-associated inflammation. Retinal macrophages can be broadly categorized into two main groups based on their origin: intrinsic macrophages situated within the retina and vitreoretinal interface and macrophages derived from infiltrating monocytes. The former comprises microglia (MG), perivascular macrophages, and macrophage-like hyalocytes. Retinal MG, as the principal population of tissue-resident population of mononuclear phagocytes, exhibits high heterogeneity and plasticity while serving as a crucial connector between retinal capillaries and synapses. This makes MG actively involved in the pathological processes across various stages of DR. Activated hyalocytes also contribute to the pathological progression of advanced DR. Additionally, recruited monocytes, displaying rapid turnover in circulation, augment the population of retinal macrophages during DR pathogenesis, exerting pathogenic or protective effect based on different subtypes. In this review, we examine novel perspectives on macrophage biology based on recent studies elucidating the diversity of macrophage identity and function, as well as the mechanisms influencing macrophage behavior. These insights may pave the way for innovative therapeutic strategies in the management of DR.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations.","authors":"Dennis Lebeda, Adrian Fierenz, Lina Werfel, Rina Rosin-Arbesfeld, Julia Hofhuis, Sven Thoms","doi":"10.1007/s00109-024-02436-6","DOIUrl":"10.1007/s00109-024-02436-6","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a neurodevelopmental disorder resulting from genetic mutations in the methyl CpG binding protein 2 (MeCP2) gene. Specifically, around 35% of RTT patients harbor premature termination codons (PTCs) within the MeCP2 gene due to nonsense mutations. A promising therapeutic avenue for these individuals involves the use of aminoglycosides, which stimulate translational readthrough (TR) by causing stop codons to be interpreted as sense codons. However, the effectiveness of this treatment depends on several factors, including the type of stop codon and the surrounding nucleotides, collectively referred to as the stop codon context (SCC). Here, we develop a high-content reporter system to precisely measure TR efficiency at different SCCs, assess the recovery of the full-length MeCP2 protein, and evaluate its subcellular localization. We have conducted a comprehensive investigation into the intricate relationship between SCC characteristics and TR induction, examining a total of 14 pathogenic MeCP2 nonsense mutations with the aim to advance the prospects of personalized therapy for individuals with RTT. Our results demonstrate that TR induction can successfully restore full-length MeCP2 protein, albeit to varying degrees, contingent upon the SCC and the specific position of the PTC within the MeCP2 mRNA. TR induction can lead to the re-establishment of nuclear localization of MeCP2, indicating the potential restoration of protein functionality. In summary, our findings underscore the significance of SCC-specific approaches in the development of tailored therapies for RTT. By unraveling the relationship between SCC and TR therapy, we pave the way for personalized, individualized treatment strategies that hold promise for improving the lives of individuals affected by this debilitating neurodevelopmental disorder. KEY MESSAGES: The efficiency of readthrough induction at MeCP2 premature termination codons strongly depends on the stop codon context. The position of the premature termination codon on the transcript influences the readthrough inducibility. A new high-content dual reporter assay facilitates the measurement and prediction of readthrough efficiency of specific nucleotide stop contexts. Readthrough induction results in the recovery of full-length MeCP2 and its re-localization to the nucleus. MeCP2 requires only one of its annotated nuclear localization signals.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRC3 attenuates osteoclastogenesis by limiting TNFα⁺ Th17 cell response in osteoporosis.","authors":"Lingyan Ren, Guangjun Liu, Yun Bai, Liling Gu, Yuan Wang, Li Sun","doi":"10.1007/s00109-024-02422-y","DOIUrl":"10.1007/s00109-024-02422-y","url":null,"abstract":"<p><p>NOD-like receptor family CARD domain containing 3 (NLRC3) is the intracellular protein belonging to NLR (NOD-like receptor) family. NLRC3 can negatively regulate inflammatory signal transduction pathways within the adaptive and innate immunocytes. However, studies need to elucidate the biological role of NLRC3 in bone remodeling. Herein, our study proved that NLRC3 prevents bone loss by inhibiting TNFα⁺ Th17 cell responses. In osteoporosis, NLRC3 attenuated TNFα⁺ Th17 cell accumulation in the bone marrow. However, osteoporosis (OP) development was aggravated without affecting bone marrow macrophage (BMM) osteoclastogenesis in NLRC3-deficient ovariectomized (OVX) mice. In this study, we transferred the wild-type and NLRC3^-/- CD4⁺ cells into Rag1^-/- mice. Consequently, we evidenced the effects of NLRC3 in CD4⁺ T cells on inhibiting the accumulation of TNFα + Th17 cells, thus restricting bone loss in the OVX mice. Simultaneously, NLRC3^-/- CD4⁺ T cells promoted the recruitment of osteoclast precursors and inflammatory monocytes into the OVX mouse bone marrow. Mechanism-wise, NLRC3 reduced the secretion of TNFα + Th17 cells of RANKL, MIP1α, and MCP1, depending on the T cells. In addition, NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. Collectively, this study appreciated the effect of NLRC3 on modulating bone mass via adaptive immunity depending on CD4⁺ cells. According to findings of this study, NLRC3 may be the candidate anti-OP therapeutic target. KEY MESSAGES: NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. NLRC3 may be the candidate anti-OP therapeutic target.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients.","authors":"Andreas Schmid, Sabine Pankuweit, Ann-Kathrin Vlacil, Sören Koch, Benedikt Berge, Praveen Gajawada, Manfred Richter, Kerstin Troidl, Bernhard Schieffer, Andreas Schäffler, Karsten Grote","doi":"10.1007/s00109-024-02426-8","DOIUrl":"10.1007/s00109-024-02426-8","url":null,"abstract":"<p><p>C1q/TNF-related protein 3 (CTRP3) represents an adipokine with various metabolic and immune-regulatory functions. While circulating CTRP3 has been proposed as a potential biomarker for cardiovascular disease (CVD), current data on CTRP3 regarding coronary artery disease (CAD) remains partially contradictory. This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). A total of 206 patients were classified into three groups: CCS (n = 64), ACS having a first acute event (ACS-1, n = 75), and ACS having a recurrent acute event (ACS-2, n = 67). The control group consisted of 49 healthy individuals. ELISA measurement in peripheral blood revealed decreased CTRP3 levels in all patient groups (p < 0.001) without significant differences between the groups. This effect was exclusively observed in male patients. Females generally exhibited significantly higher CTRP3 plasma levels than males. ROC curve analysis in male patients revealed a valuable predictive potency of plasma CTRP3 in order to identify CAD patients, with a proposed cut-off value of 51.25 ng/mL. The sensitivity and specificity of prediction by CTRP3 were congruent for the subgroups of CCS, ACS-1, and ACS-2 patients. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings, with male mice exhibiting higher circulating CTRP3 levels than females. We conclude that circulating CTRP3 levels are decreased in both male CCS and ACS patients. Therefore, CTRP3 might be useful as a biomarker for CAD but not for distinguishing an acute from a chronic setting. KEY MESSAGES: CTRP3 levels were found to be decreased in both male CCS and ACS patients compared to healthy controls. Plasma CTRP3 has a valuable predictive potency in order to identify CAD patients among men and is therefore proposed as a biomarker for CAD but not for distinguishing between acute and chronic settings. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings in men.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Hsp70 promoter-based mouse for heat shock-induced gene modulation.","authors":"Hangang Chen, Yangli Xie, Mei Zhang, Junlan Huang, Wanling Jiang, Ruobin Zhang, Can Li, Xiaolan Du, Hua Chen, Qiang Nie, Sen Liang, Qiaoyan Tan, Jing Yang, Min Jin, Shuo Huang, Liang Kuang, Nan Su, Huabing Qi, Xiaoqing Luo, Xiaoling Xu, Chuxia Deng, Lin Chen, Fengtao Luo","doi":"10.1007/s00109-024-02433-9","DOIUrl":"10.1007/s00109-024-02433-9","url":null,"abstract":"<p><p>Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting the therapeutic potential of contracting skeletal muscle-released extracellular vesicles in cancer: Current insights and future directions.","authors":"Ana Carolina Pinto, Patrícia Tavares, Bruno Neves, Pedro F Oliveira, Rui Vitorino, Daniel Moreira-Gonçalves, Rita Ferreira","doi":"10.1007/s00109-024-02427-7","DOIUrl":"10.1007/s00109-024-02427-7","url":null,"abstract":"<p><p>The health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases after physical exercise or how muscle contraction modulates the secretory activity of other tissues and thus influences the content and profile of circulating EVs. Furthermore, the destination of EVs after exercise is unknown, and it depends on their molecular composition, particularly adhesion proteins. The cargo of EVs is influenced by the training program, with acute training sessions having a greater impact than chronic adaptations. Indeed, there are numerous questions regarding the role of EVs in mediating the effects of exercise, the clarification of which is critical for tailoring exercise training prescriptions and designing exercise mimetics for patients unable to engage in exercise programs. This review critically analyzes the current knowledge on the effects of exercise on the content and molecular composition of circulating EVs and their impact on cancer progression.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological and pathological effects of phase separation in the central nervous system.","authors":"Jiaxin Wang, Hongrui Zhu, Ruijia Tian, Qian Zhang, Haoliang Zhang, Jin Hu, Sheng Wang","doi":"10.1007/s00109-024-02435-7","DOIUrl":"10.1007/s00109-024-02435-7","url":null,"abstract":"<p><p>Phase separation, also known as biomolecule condensate, participates in physiological processes such as transcriptional regulation, signal transduction, gene expression, and DNA damage repair by creating a membrane-free compartment. Phase separation is primarily caused by the interaction of multivalent non-covalent bonds between proteins and/or nucleic acids. The strength of molecular multivalent interaction can be modified by component concentration, the potential of hydrogen, posttranslational modification, and other factors. Notably, phase separation occurs frequently in the cytoplasm of mitochondria, the nucleus, and synapses. Phase separation in vivo is dynamic or stable in the normal physiological state, while abnormal phase separation will lead to the formation of biomolecule condensates, speeding up the disease progression. To provide candidate suggestions for the clinical treatment of nervous system diseases, this review, based on existing studies, carefully and systematically represents the physiological roles of phase separation in the central nervous system and its pathological mechanism in neurodegenerative diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}