Current Issues in Molecular Biology最新文献

{"title":"Effects of a Three-Day vs. Six-Day Exposure to Normobaric Hypoxia on the Cardiopulmonary Function of Rats.","authors":"Charly Bambor, Sarah Daunheimer, Coralie Raffort, Julia Koedel, Aida Salameh, Beate Raßler","doi":"10.3390/cimb47020125","DOIUrl":"10.3390/cimb47020125","url":null,"abstract":"<p><p>In rats, normobaric hypoxia significantly reduced left ventricular (LV) inotropic function while right ventricular (RV) function was not impaired. In parallel, the animals developed pulmonary edema and inflammation. In the present study, we investigated whether cardiac function and pulmonary injury would aggravate after three and six days of hypoxia exposure or whether cardiopulmonary reactions to prolonged hypoxia would become weaker due to hypoxic acclimatization. Sixty-four female rats were exposed for 72 or 144 h to normoxia. They received a low-rate infusion (0.1 mL/h) with 0.9% NaCl solution. We evaluated indicators of the general condition, blood gas parameters, and hemodynamic function of the rats. In addition, we performed histological and immunohistochemical analyses of the lung. Despite a significant increase in hemoglobin concentration, the LV function deteriorated with prolonged hypoxia. In contrast, the RV systolic pressure and contractility steadily increased by six days of hypoxia. The pulmonary edema and inflammation persisted and rather increased with prolonged hypoxia. Furthermore, elevated protein concentration in the pleural fluid indicated capillary wall stress, which may have aggravated the pulmonary edema. In conclusion, six days of hypoxia and NaCl infusion place significant stress on the cardiopulmonary system of rats, as is also reflected by the 33% of premature deaths in this rat group.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer's Disease.","authors":"Milan M Medd, Jayden E Yon, Hongxin Dong","doi":"10.3390/cimb47020124","DOIUrl":"10.3390/cimb47020124","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline and loss of neuronal integrity. Emerging evidence suggests that RhoA, Rho-associated coiled-coil kinase (ROCK), and their downstream effector molecule glycogen synthase 3β (GSK3β) interact within a complex signaling pathway (RhoA/ROCK/GSK3β) that plays a crucial role in the pathogenesis of AD. RhoA, a small GTPase, along with its downstream effector, ROCK, regulates various cellular processes, including actin cytoskeleton dynamics, apoptosis, and synaptic plasticity. GSK3β, a serine/threonine kinase, plays a key role in neuronal function and AD pathology, including the regulation of tau phosphorylation and amyloid-beta cleavage. Overactive GSK3β has been closely linked to tau hyperphosphorylation, neurodegeneration, and the progression of AD. Thus, GSK3β has been considered as a promising therapeutic target for treating AD and mitigating cognitive impairment. However, clinical trials of GSK3β in AD have faced considerable challenges due to the complexity of the specific neuronal inhibition of GSK3β. In this review, we summarize the literature regarding the relationship of RhoA/ROCK and GSK3β signaling pathways in AD pathogenesis. We further discuss recent findings of the sTREM2-transgelin-2 (TG2) axis as a potential mediator of this complex pathway and provide our review on a novel targeting strategy for AD.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EpCAM Signaling in Oral Cancer Stem Cells: Implications for Metastasis, Tumorigenicity, and Therapeutic Strategies.","authors":"Chuan-Hsin Chang, Chung-Che Tsai, Fu-Ming Tsai, Tin-Yi Chu, Po-Chih Hsu, Chan-Yen Kuo","doi":"10.3390/cimb47020123","DOIUrl":"10.3390/cimb47020123","url":null,"abstract":"<p><p>Oral cancer, a subtype of head and neck cancer, poses significant global health challenges owing to its late diagnosis and high metastatic potential. The epithelial cell adhesion molecule (EpCAM), a transmembrane glycoprotein, has emerged as a critical player in cancer biology, particularly in oral cancer stem cells (CSCs). This review highlights the multifaceted roles of EPCAM in regulating oral cancer metastasis, tumorigenicity, and resistance to therapy. EpCAM influences key pathways, including Wnt/β-catenin and EGFR, modulating CSC self-renewal, epithelial-to-mesenchymal transition (EMT), and immune evasion. Moreover, EpCAM has been implicated in metabolic reprogramming, epigenetic regulation, and crosstalk with other signaling pathways. Advances in EpCAM-targeting strategies, such as monoclonal antibodies, chimeric antigen receptor (CAR) T/NK cell therapies, and aptamer-based systems hold promise for personalized cancer therapies. However, challenges remain in understanding the precise mechanism of EpCAM in CSC biology and its translation into clinical applications. This review highlights the need for further investigation into the role of EPCAM in oral CSCs and its potential as a therapeutic target to improve patient outcomes.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of PD-L1 and HIF-1 Alpha Expression with KRAS Mutation and Clinicopathological Parameters in Non-Small Cell Lung Cancer.","authors":"Seda Er Özilhan, Safa Can Efil, Doğukan Çanakçı, Yetkin Ağaçkıran, Didem Şener Dede, Nilüfer Onak Kandemir, Mehmet Doğan, Tuba Dilay Kökenek Ünal, Merve Meryem Kıran, Serra Kayaçetin, Hilal Balta, Hayriye Tatlı Doğan","doi":"10.3390/cimb47020121","DOIUrl":"10.3390/cimb47020121","url":null,"abstract":"<p><p><b>Background:</b> Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinomas (NSCLCs) comprising the majority of cases. Among the common driver mutations, KRAS plays a critical role in guiding treatment strategies. This study evaluates the expression of programmed death-ligand 1 (PD-L1) and hypoxia-inducible factor 1-alpha (HIF-1α) in <i>KRAS</i>-mutant NSCLCs and investigates their associations with clinicopathological findings. <b>Methods:</b> A total of 85 cases with <i>KRAS</i> mutations were analyzed. Immunohistochemical staining for HIF-1α and PD-L1 was performed, and their relationships with mutation status and prognostic variables were assessed. <b>Results:</b> A significant correlation was identified between HIF-1α expression and PD-L1 expression in tumor cells. While the <i>KRAS</i> G12C mutation was not significantly associated with HIF-1α expression in tumor cells, it demonstrated a notable relationship with HIF-1α expression in the tumor microenvironment and PD-L1 expression. However, PD-L1 and HIF-1α expression did not significantly influence overall survival outcomes. <b>Conclusions:</b> Expression of PD-L1 was positively correlated with HIF-1α, which may provide evidence for a novel therapy targeting PD-L1 and HIF-1α in NSCLC. Further comprehensive studies are warranted to elucidate the prognostic implications of tumor-microenvironment and mutation interactions.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS Mutation Status in Relation to Clinicopathological Characteristics of Romanian Colorectal Cancer Patients.","authors":"Elena-Roxana Avădănei, Irina-Draga Căruntu, Irina Nucă, Raluca Anca Balan, Ludmila Lozneanu, Simona-Eliza Giusca, Diana Lavinia Pricope, Cristina Gena Dascalu, Cornelia Amalinei","doi":"10.3390/cimb47020120","DOIUrl":"10.3390/cimb47020120","url":null,"abstract":"<p><p>Our study's aim was to evaluate the clinicopathological profile of colorectal cancer (CRC) patients from North-East Romania in relation to the Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>). We designed a retrospective study on 108 CRC patients using the fully automated real-time PCR-based molecular testing system, Idylla^TM<i>KRAS</i> Mutation Test (Biocartis, Mechelen, Belgium). Of the patients, 64 (59.3%) were men and 62 (57.4%) were older than the group average, with left bowel location in 38 cases (35.2%), adenocarcinoma NOS in 102 cases (94.4%), mixed histological pattern in 65 cases (60.2%), T3 in 60 patients (55.6%), N2 in 46 patients (42.6%), and 7-12 tumour buds registered in 58 tumours (53.7%). A total of 54 tumour samples (50%) showed <i>KRAS</i> mutation. Statistical comparative analyses associated <i>KRAS</i> mutations with the histopathological pattern (<i>p</i> = 0.018), tumour grade (<i>p</i> = 0.030), depth of invasion (pT) (<i>p</i> < 0.001), lymph node involvement (pN) (<i>p</i> < 0.001), venous vascular invasion (<i>p</i> = 0.048), and tumour buds' number (<i>p</i> = 0.007). Our results demonstrate the relationship between <i>KRAS</i> mutation and clinicopathological features, with possible impact in clinical tumour stratification and therapeutic management.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Studies on the Effects of Static Magnetic Fields (SMF) on Reproductive Function.","authors":"Chengchang Zhang, Chengle Dong, Xiaohang Liu, Jiaxing Zhang, Qinlan Li, Shuting Chen, Hu Zhao, Donghui Huang","doi":"10.3390/cimb47020116","DOIUrl":"10.3390/cimb47020116","url":null,"abstract":"<p><strong>Background: </strong>With the widespread use of static magnetic fields (SMFs) in applications such as magnetic resonance imaging (MRI) and electric vehicles, concerns have arisen regarding their potential effects on reproductive health. Despite increasing research, the impact of SMFs on reproductive function remains a subject of debate, requiring further exploration.</p><p><strong>Methods: </strong>This review synthesizes animal and clinical studies on the effects of SMF on reproductive function. It examines various SMF intensities and exposure durations, focusing on mitochondrial function, chromosomal division, and embryonic development.</p><p><strong>Results: </strong>The review reveals that low-intensity SMF exposure adversely affects mitochondrial function in sperm and eggs, reducing their activity. It also impacts follicular cells, delaying chromosomal division. Medium- and high-intensity SMF exposure shows mixed results, with both potential benefits and risks, requiring further research. High-intensity SMFs may pose teratogenic risks to embryos and delay the development of fertilized eggs. The position of SMF exposure also matters, likely due to field non-uniformity.</p><p><strong>Conclusions: </strong>This review provides a foundation for further investigation into the effects of SMFs on reproductive function, highlighting the need for more comprehensive studies to assess safety and applications. Special caution is advised for pregnant women regarding SMF exposure, given its potential risks.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Efficacy and Target Genes of <i>Atractylodes Macrocephala Koidz</i> Against Alzheimer's Disease Based on Multi-Omics, Computational Chemistry, and Experimental Verification.","authors":"Yuanteng Zheng, Xin Gao, Jiyang Tang, Li Gao, Xiaotong Cui, Kechun Liu, Xiujun Zhang, Meng Jin","doi":"10.3390/cimb47020118","DOIUrl":"10.3390/cimb47020118","url":null,"abstract":"<p><strong>Objective: </strong>To unveil the efficacy and ferroptosis-related mechanisms of <i>Atractylodes Macrocephala Koidz</i> (AMK) against Alzheimer's disease (AD), which is the most widespread neurodegenerative disease.</p><p><strong>Methods: </strong>Gene set variation analysis (GSVA) scores were used to investigate the relationship between ferroptosis and AD. Logistic regression with seven feature selections and a deep learning model were utilized to identify potential targets of AMK based on transcriptomic data from multiple tissues. A transcriptome-wide association study (TWAS), summary-data-based mendelian randomization (SMR), and mendelian randomization (MR) were utilized to validate the causal relationship between target genes and AD risk. A single-gene gene set enrichment analysis (GSEA) was employed to investigate the biological pathways associated with the target genes. Three molecular docking strategies and a molecular dynamics simulation were employed to verify the binding domains interacting with AMK. Furthermore, the anti-AD effects of AMK were validated in a zebrafish AD model by testing behavior responses, apoptosis, and the deposition of beta-amyloid (Aβ) in the brain. Ultimately, real-time qPCR was used to verify the ferroptosis-related targets, which was identified via multi-omics.</p><p><strong>Results: </strong>Ferroptosis is an important pathogenic mechanism of AD, as suggested by the GSVA scores. AMK may exert its anti-AD activity through targets genes identified in the brain (<i>ATP5MC3, GOT1, SAT1, EGFR</i>, and <i>MAPK9</i>) and blood (<i>G6PD, PGD, ALOX5, HMOX1,</i> and <i>ULK1</i>). <i>EGFR</i> and <i>HMOX1</i> were further confirmed as target genes mediating the anti-AD activity of AMK through TWAS, SMR, and MR analyses. The GSEA results indicated that <i>EGFR</i> may be involved in oxidative phosphorylation-related pathways, while <i>HMOX1</i> may be associated with lysosome and phagosome pathways. The results of three molecular docking strategies and molecular dynamics simulations implied that the kinase domain of EGFR and the catalytic domain of HMOX1 played pivotal roles in the interaction between AMK and the targets. In a zebrafish model, AD-like symptoms including motor slowness and delayed responses, neuronal apoptosis, and plaque deposition in the brain, were significantly improved after AMK treatment. Accordingly, AMK reversed the abnormal expression of <i>egfra</i> and <i>hmox1a</i>, two core targets genes involved in ferroptosis.</p><p><strong>Conclusions: </strong>AMK significantly alleviated AD-like symptoms through the modulation of EGFR and HMOX1, which might reduce lipid peroxidation, thereby suppressing ferroptosis. This study provided evidence supporting the efficacy and therapeutic targets associated with ferroptosis in AMK-treated AD, which aid in the development of therapeutic interventions.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Volatile Metabolome and Transcriptome in Sweet Basil Under Drought Stress.","authors":"Yuan Zhou, Guangying Ma, Wenlue Li, Lupeng Xie, Shuxia Zhan, Xingda Yao, Ziwei Zuo, Danqing Tian","doi":"10.3390/cimb47020117","DOIUrl":"10.3390/cimb47020117","url":null,"abstract":"<p><p>Basil, renowned for its aromatic properties, exhibits commendable drought tolerance and holds significant value as an edible and medicinal plant. Recognizing the scarcity of studies addressing basil's response to drought stress, we performed physiological experiments and omics analyses of sweet basil across four distinct levels of drought stress. During drought stress, basil showed increased activity of antioxidant enzymes and accumulated more osmoregulatory compounds. Our metabolic analysis meticulously identified a total of 830 metabolites, among which, 215 were differentially accumulated. The differentially accumulated metabolites under drought stress were predominantly esters and terpenes; however, none were identified as the primary volatile compounds of basil. Transcriptome analyses highlighted the pivotal roles of phenylpropanoid and flavonoid biosynthesis and lipid metabolism in fortifying the resistance of sweet basil against drought stress. α-linolenic acid, lignin, flavonoid, and flavonol contents significantly increased under stress; the essential genes involved in the production of these compounds were confirmed through quantitative real-time PCR (qRT-PCR), and their variations aligned with the outcomes from sequencing. This holistic approach not only enriches our understanding of the molecular intricacies underpinning basil's drought resistance but also furnishes valuable insights for the molecular breeding of basil varieties endowed with enhanced drought tolerance.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.","authors":"Debora Baroni","doi":"10.3390/cimb47020119","DOIUrl":"10.3390/cimb47020119","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride and bicarbonate channel localized on the plasma membrane of epithelial cells. Over the last three decades, high-throughput screening assays have been extensively employed in identifying drugs that target specific defects arising from CFTR mutations. The two main categories of such compounds are potentiators, which enhance CFTR gating by increasing the channel's open probability, and correctors, which improve CFTR protein folding and trafficking to the plasma membrane. In addition to these, other investigational molecules include amplifiers and stabilizers, which enhance the levels and the stability of CFTR on the cell surface, and read-through agents that promote the insertion of correct amino acids at premature termination codons. Currently, four CFTR modulators are clinically approved: the potentiator ivacaftor (VX-770), either as monotherapy or in combination with the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). Among these, the triple combination VX-445/VX-661/VX-770 (marketed as Trikafta^® in the US and Kaftrio^® in Europe) has emerged as the most effective CFTR modulator therapy to date, demonstrating significant clinical benefits in phase III trials for patients with at least one F508del CFTR allele. Despite these advancements, the mechanisms of action and binding sites of these modulators on CFTR have only recently begun to be elucidated. A deeper understanding of these mechanisms could provide essential insights for developing more potent and effective modulators, particularly in combination therapies. This narrative review delves into the mechanism of action, binding sites, and combinatorial effects of approved and investigational CFTR modulators, highlighting ongoing efforts to broaden therapeutic options for individuals with CF.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.","authors":"Ilinca Savulescu-Fiedler, Luiza-Roxana Dorobantu-Lungu, Serban Dragosloveanu, Serban Nicolae Benea, Christiana Diana Maria Dragosloveanu, Ana Caruntu, Andreea-Elena Scheau, Constantin Caruntu, Cristian Scheau","doi":"10.3390/cimb47020115","DOIUrl":"10.3390/cimb47020115","url":null,"abstract":"<p><p>Cholesterol is an essential element for the development and normal function of the central nervous system. While peripheral cholesterol is influenced by liver metabolism and diet, brain cholesterol metabolism takes place in an isolated system due to the impermeability of the blood-brain barrier (BBB). However, cross-talk occurs between the brain and periphery, specifically through metabolites such as oxysterols that play key roles in regulating cholesterol balance. Several neurodegenerative conditions such as Alzheimer's disease or Parkinson's disease are considered to be affected by the loss of this balance. Also, the treatment of hypercholesterolemia needs to consider these discrete interferences between brain and peripheral cholesterol and the possible implications of each therapeutic approach. This is particularly important because of 27-hydroxycholesterol and 24-hydroxycholesterol, which can cross the BBB and are involved in cholesterol metabolism. This paper examines the metabolic pathways of cholesterol metabolism in the brain and periphery and focuses on the complex cross-talk between these metabolisms. Also, we emphasize the regulatory role of the BBB and the need for an integrated approach to cholesterol management.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}