Biochemical Genetics最新文献

{"title":"Expression of Transforming Growth Factor Beta 1 in Lung Adenocarcinoma and Its Relationship with Circulating Tumour Cells.","authors":"Ning Chen, Duo-Jun Qiu, Jian-Zhu Yang, Gui-Yun Zhu, Li-Fei Kang, Xiao-Ying An, Zhi-Ming Xu, Xiao-Xia Li","doi":"10.1007/s10528-026-11420-3","DOIUrl":"https://doi.org/10.1007/s10528-026-11420-3","url":null,"abstract":"<p><p>To investigate the relationship between the expression of transforming growth factor beta 1 (TGF-β1), epithelial-mesenchymal transition (EMT)-related proteins, circulating tumour cells (CTCs) positivity rate and tumour differentiation degree in lung adenocarcinoma. A prospective study was conducted, including 78 patients with lung adenocarcinoma who underwent surgical resection at our hospital between March 2021 and December 2021. Clinical data, lung adenocarcinoma and adjacent tissues were collected. Western blot, immunohistochemistry and RT-PCR were used to detect the expression of TGF-β1, EMT-related proteins (E-cadherin, vimentin) and mRNA in lung adenocarcinoma. Peripheral blood for CTC analysis was collected within 1 week before surgical resection. Pearson correlation analysis was employed to assess the relationship between TGF-β1, EMT and CTCs. There was a significant correlation between the positive rate of CTCs and the degree of tumour differentiation in patients with lung adenocarcinoma (P < 0.05). The expression of TGF-β1 increased significantly as the degree of differentiation decreased (P < 0.05). It was positively correlated with vimentin expression and negatively correlated with E-cadherin expression (P < 0.05). High expression of TGF-β1 in lung adenocarcinoma promotes EMT and the occurrence of CTCs and is associated with the degree of tumour differentiation.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Exercise in Regulating Histone Modifications and Non-coding RNAs in Muscle Aging and Sarcopenia.","authors":"Junli Wang, Junhua Li","doi":"10.1007/s10528-026-11418-x","DOIUrl":"https://doi.org/10.1007/s10528-026-11418-x","url":null,"abstract":"<p><p>Sarcopenia, the progressive loss of skeletal muscle mass and function with age, is a major contributor to frailty and decreased quality of life in older adults. While physical exercise remains the most effective intervention, its molecular mechanisms of action are not fully understood. Emerging evidence highlights the central role of epigenetic regulation-including histone modifications and non-coding RNAs (ncRNAs)-in mediating both the pathogenesis of sarcopenia and the adaptive responses to exercise. This review synthesizes current findings on how aging disrupts the epigenetic landscape of skeletal muscle, fostering anabolic resistance, inflammation, and impaired regeneration. We explore how exercise reverses these effects by modulating histone acetylation, methylation, and the novel mark of lactylation, thereby reactivating key genes involved in muscle maintenance and repair. Additionally, we detail how specific microRNAs and long non-coding RNAs contribute to muscle plasticity, and how their dysregulation underlies age-related functional decline. Importantly, we emphasize the interplay between histone modifiers and ncRNAs, and the translational evidence from human trials supporting exercise as an epigenetic reprogramming agent. Although human evidence is limited compared to animal models, emerging clinical studies in older adults demonstrate that resistance and endurance training modulate histone acetylation/methylation and miRNA profiles, with dose-dependent benefits on muscle function and epigenetic markers (e.g., reduced epigenetic age acceleration via methylation clocks in active elderly). These insights offer promising avenues for therapeutic strategies aimed at extending healthspan and combating sarcopenia in aging populations.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between SGK1 Expression Level and Multiple Myeloma Progression After Autologous Hematopoietic Stem Cell Transplantation.","authors":"Ting Fan, Caili Guo, Ying Zhang, Jianna Yao, Yanli Yu, Xiaoning Wang","doi":"10.1007/s10528-026-11422-1","DOIUrl":"https://doi.org/10.1007/s10528-026-11422-1","url":null,"abstract":"<p><p>To explore the correlation between serum and glucocorticoid inducible kinase-1 (SGK1) expression levels and the multiple myeloma (MM) progression in patients after autologous stem cell transplantation (ASCT). A total of 100 MM patients who received ASCT in the Hematology Department of our hospital during January 2020 to December 2022 were selected as the research subjects. The mRNA level of SGK1 was detected by RT-PCR. Taking the median relative expression level of SGK1 mRNA (2.15) as the critical value, these subjects were divided into SGK1 high expression group (SGK1 mRNA ≥ 2.15, n = 43) and SGK1 low expression group (SGK1 mRNA < 2.15, n = 57). The expression level of SGK1 was detected by IHC. The correlation was analyzed by Spearman correlation coefficient. The survival curve drawn through Kaplan-Meier method was further verified using Log-rank test. Cox proportional hazard regression model was used for multivariate analysis to screen independent risk factors. The receiver's working characteristic (ROC) curve was drawn to evaluate the predictive value. The H-Score was significantly higher in the SGK1 high expression group (8.52 ± 2.13) than the low expression group (3.27 ± 1.68) (t = 11.240, P < 0.001). After induction therapy, SGK1 high expression group had much lower proportion of achieving complete remission (CR), and markedly higher serum levels of β2-MG and LDH than SGK1 low expression group (P < 0.05). The expression of SGK1 in patients with partial remission (PR) was significantly higher than those with CR and very good partial remission (VGPR) (P < 0.01). Median TTP, median PFS and median OS were significantly lower in SGK1 high expression group than the SGK1 low expression group (Log-rank P < 0.01). Three months after transplantation, the positive rate of Minimal residual disease (MRD) was 48.84% (21/43) in SGK1 high expression group and 22.81% (13/57) in SGK1 low expression group (P < 0.01). The expression level of SGK1 was positively correlated with serum β2-MG (r = 0.452, P < 0.01), LDH (r = 0.388, P < 0.01), the proportion of plasma cells in bone marrow (r = 0.321, P < 0.01), and pre-transplant remission status (CR = 1, VGPR = 2, PR = 3; r = 0.413, P < 0.01), but negatively correlated with PFS (r= - 0.527, P < 0.01) and OS (r= - 0.482, P < 0.01). High SGK1 expression, serum β2-MG, and positive LDH and MRD were independent risk factors (P < 0.05). The ROC curve analysis of predicting disease progression after transplantation based on the relative expression level of SGK1 mRNA showed the area under the curve (AUC) of 0.883 (95% CI: 0.785-0.934), an optimal cutoff value of 2.18, a sensitivity of 94.32%, and a specificity of 73.63%. High expression of SGK1 was an independent risk factor for disease progression after ASCT in MM patients, which was closely related to the short survival time and high MRD positive rate. The expression level of SGK1 had a certain predictive effect on the disease progression after transplantation.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VALD-3 Induces GSDME-Dependent Pyroptosis via ROS/JNK/Bax Pathway in Triple-Negative Breast Cancer Cells.","authors":"Xuhui Zhao, Xuhong Pan, Weijie Ma, Shuang Liang, Dezhuan Da, Jiawei Liu, LingFang Zhang, Pengfei Song, Hongling Li","doi":"10.1007/s10528-026-11423-0","DOIUrl":"https://doi.org/10.1007/s10528-026-11423-0","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, known for its high malignancy, elevated risk of recurrence and metastasis, and limited therapeutic options, resulting in the poorest prognosis among breast cancer types. This study explores the anticancer effects of VALD-3, a Schiff base ligand derivative, on breast cancer cells. While VALD-3 exhibited cytotoxic effects on both triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER+) MCF-7 cells, it more potently inhibited TNBC cell viability. More importantly, VALD-3 induced characteristic pyroptotic features selectively in TNBC cells, including cell swelling, balloon-like protrusions, and the release of inflammatory cytokines due to pore formation in the plasma membrane, ultimately inhibiting tumor growth. Mechanistically, VALD-3 increased reactive oxygen species (ROS) levels and JNK phosphorylation, leading to the recruitment of Bax to the mitochondria and the formation of a Bax-Bcl-2 heterodimer, which facilitated cytochrome c release into the cytoplasm. This cascade activated caspase-3 and triggered gasdermin E(GSDME)- dependent pyroptosis in TNBC cells. Thus, VALD-3 treatment initiated the ROS/JNK/Bax-mitochondrial apoptosis pathway, leading to caspase-3 activation and GSDME cleavage, thereby executing pyroptosis. These findings suggest that GSDME-dependent pyroptosis is a novel mechanism by which VALD-3 eradicates cancer cells and offer new insights into potential clinical applications for anticancer therapies.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Genetic Risk Factors in Recurrent Pregnancy Loss: An Integrative Chromosomal and Bioinformatics Approach.","authors":"Shivani Mishra, Ashish Ashish, Sangeeta Rai, Abhay Kumar Yadav, Royana Singh","doi":"10.1007/s10528-026-11424-z","DOIUrl":"https://doi.org/10.1007/s10528-026-11424-z","url":null,"abstract":"<p><p>Recurrent pregnancy loss (RPL) is characterized by two or more consecutive pregnancy losses, often associated with genetic, immunological, endocrine, and anatomical abnormalities. Among these, chromosomal abnormalities, including aneuploidies and submicroscopic copy number variations (CNVs), play a critical role in adverse pregnancy outcomes. A total of 125 fetal specimens were collected, of which 118 were included after applying predefined exclusion criteria. DNA isolated from products of conception and fetal tissues was subjected to quantitative fluorescent PCR (QF-PCR) for rapid aneuploidy screening. A subset of 30 samples with selected QF-PCR outcomes underwent array comparative genomic hybridization (aCGH). Identified CNVs were interpreted according to ACMG/ClinGen guidelines, followed by bioinformatics analyses using FunRich, WebGestalt, KEGG, and STRING to explore functional annotations and pathway enrichment. Among 118 samples, QF-PCR identified aneuploidy in 36 cases (30.5%), including monosomy (n = 20) and trisomy (n = 16), while 82 cases were reported as normal. Maternal age showed a significant association with chromosomal abnormalities (p < 0.05), and a weak negative correlation was observed between gestational age and aneuploidy risk (r = - 0.238, p = 0.008855). In the aCGH cohort (n = 30), clinically relevant CNVs were identified, including pathogenic and likely pathogenic variants, as well as variants of uncertain significance (VOUS). Notably, genes such as CFHR3, TNFRSF4, UGT2B17, CD24, MSR1, and the PSG gene family were implicated. Functional enrichment analysis revealed involvement in immune-inflammatory pathways, endocrine regulation, lipid metabolism, extracellular matrix remodeling, and placental development. This study demonstrates the enhanced diagnostic utility of combining aCGH with QF-PCR for identifying chromosomal abnormalities in RPL. However, the observed associations between CNVs and biological pathways are exploratory in nature and require validation in larger, well-powered cohorts.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome-Level Genome Assembly of the Sea Urchin Glyptocidaris crenularis and Sex Chromosome Identification.","authors":"Quanchao Wang, Wanlong Sun, Yufeng Zhai, Yue Wang, Xiaojing Li, Hena Ji, Jing Yu, Rongrong Gao, Zenglei Song, Qian Zhang","doi":"10.1007/s10528-026-11421-2","DOIUrl":"https://doi.org/10.1007/s10528-026-11421-2","url":null,"abstract":"<p><p>The economic importance of the sea urchin Glyptocidaris crenularis drives the need to elucidate the genetic mechanisms controlling its sex differentiation and development, a key step for enabling targeted genetic improvement. This study presents a chromosome-scale genome assembly for G. crenularis characterized by 22 chromosome-length scaffolds and a total length of 787.45 Mb. The phylogenetic tree revealed that G. crenularis diverged early among sea urchins. Synteny analysis among species suggested that superscaffold 10 might be the sex chromosome. Subsequent transcriptomic profiling further revealed 273 genes (298 transcripts) on chromosome 10 whose expression differed significantly between testis and ovary tissues. The genomic resources established in this study provide a foundation for investigating the population genetics, evolution, and functional mechanisms of this species, while the identified sex chromosomes and candidate genes pave the way for elucidating the molecular basis of sex determination in sea urchins.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Diversity and Population Structure of 72 Turkish Ficus carica (L.) Genotypes Assessed Using SCoT Markers.","authors":"Meliha Feryal Sarıkaya, Muhammad Azhar Nadeem, Sarmad Ali Qureshi, Mehmet Bedir, Muhammed Tatar, Amjad Ali, Muhammad Tanveer Altaf, Viyan Acar Uçer, Kağan Kökten, Erdal Aglar, Faheem Shehzad Baloch","doi":"10.1007/s10528-026-11419-w","DOIUrl":"10.1007/s10528-026-11419-w","url":null,"abstract":"<p><p>Ficus carica L. is an economically important fruit crop widely cultivated in the Mediterranean region. In this study, genetic diversity and population structure were investigated in 72 F. carica genotypes collected from the Derecik and Çukurca regions of Hakkâri province, Türkiye, using 15 highly polymorphic Start Codon Targeted (SCoT) markers. A total of 481 amplification bands were obtained, of which 475 were polymorphic, resulting in a high average polymorphism rate of 98.60%. Genetic diversity indices indicated substantial variation among the genotypes, with a mean effective number of alleles of 1.53, gene diversity of 0.31, and Shannon information index of 0.47. The average genetic distance among genotypes was 0.37, with the highest pairwise distance (0.721) observed between genotypes HC4 and HD7. Analysis of molecular variance (AMOVA) revealed that most genetic variation was distributed within populations (93%), whereas only 7% was among populations. Bayesian STRUCTURE analysis identified two distinct genetic clusters corresponding largely to geographic origin, with 22 genotypes (30.56%) classified as admixed based on a membership coefficient threshold of < 0.70. Principal coordinate analysis (PcoA) clearly separated genotypes according to their sampling locations, where Axis 1 and Axis 2 explained 24.31% and 15.07% of the total genetic variation, respectively. Overall, these findings demonstrate the effectiveness of SCoT markers in assessing genetic diversity and population structure in F. carica germplasm from southeastern Türkiye. Future studies should use codominant markers (SSRs and SNPs) expand geographic sampling, and adopt open data repositories to enhance conservation and breeding strategies.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population.","authors":"Konstantinos Rouskas, David Meyre, Stephane Lobbens, Dimitrios Papazoglou, Anastasia Kouvatsi, Philippe Froguel","doi":"10.1007/s10528-026-11413-2","DOIUrl":"https://doi.org/10.1007/s10528-026-11413-2","url":null,"abstract":"<p><p>The ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) gene, encoding a protein that negatively modulates insulin receptor activation, remains relatively understudied in obesity genetics. K121Q (rs1044498; chr6:132,172,368: A > C) and other ENPP1 genetic variants (rs1799774; chr6:132,203,471: insT> delT and rs7754561; chr6:132,212,694: A > G), as well as the risk haplotype Q-delT-G have been investigated for their association with obesity risk mostly in populations from Central and Northern Europe, yielding controversial findings. Given the significance of reproducibility in genetic association studies and the scarcity of data from Southern Europe, we performed a case-control replication study to test the hypothesis that ENPP1 variants and haplotypes are associated with severe obesity in the underexplored and high-risk Greek population. A total of 979 Greek individuals (mean age: 47.6 ± 12.5years old), including 510 adults with severe obesity (BMI≥35Kg/m²) and 469 normal-weight (18.5 < BMI<25Kg/m²) controls, were studied. Three ENPP1 variants (rs1044498, rs1799774 and rs7754561) were genotyped using the TaqMan allelic discrimination assay. Logistic regression was applied to detect association of variants with obesity. Linkage disequilibrium among the three variants was assessed, and haplotype frequencies were compared between groups. The three variants did not exhibit any association with adult severe obesity. The three variants were in partial linkage disequilibrium (r² ≤ 0.43). ENPP1 haplotype distribution differed significantly between normal-weight individuals and those with adult severe obesity (likelihood ratio x² = 13.38, P = 0.020), with the Q-delT-G haplotype found to be present exclusively in individuals with adult severe obesity (frequency 3.3%) and to be associated with adult severe obesity (x² = 5.66, P = 0.017; reference haplotype K-InsT-A, consisting of the three major alleles of the three variants). Our replication findings contribute novel evidence regarding the genetic architecture of adult severe obesity in a Southern-European population, however larger studies are necessary to validate these results.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Splice-Site Variant in ACY1 Associated with Congenital Hearing Loss: Clinical, Biochemical, and Zebrafish Functional Evidence.","authors":"Sha Yu, Zhenmin Xu, Huijun Wang, Liheng Chen, Shao Wei Hu, Yunfei Zhang, Huiying Lyu, Hongjiang Wu, Mengyuan Wu, Yilai Shu, Wenxia Chen","doi":"10.1007/s10528-026-11417-y","DOIUrl":"https://doi.org/10.1007/s10528-026-11417-y","url":null,"abstract":"<p><p>Variants in the aminoacylase 1 (ACY1) gene are associated with diverse clinical phenotypes, but their roles in hearing loss remain unclear. This study aimed to investigate the potential role of ACY1 in hearing loss. Exome sequencing was performed on 396 patients with sensorineural hearing loss. We identified a homozygous splicing variant, c.1063-1G>A, in ACY1 as a plausible candidate variant in a 5-year-old girl with congenital hearing loss and normal developmental milestones over a 4-year follow-up. Functional assays, including urinary organic acid analysis and aminoacylase 1 enzyme activity testing in Epstein-Barr virus (EBV)-transformed lymphoblasts, confirmed aminoacylase 1 deficiency in the patient. In vitro splicing assays showed that the c.1063-1G>A variant activated a cryptic splice site, causing aberrant splicing, a frameshift, and a premature stop codon. A zebrafish model with morpholino-mediated acy1 knockdown revealed a significant reduction in hair cells and impaired auditory function, which were effectively rescued by wild-type but not mutant human ACY1 mRNA. Furthermore, transcriptomic profiling of zebrafish auditory hair cells, combining fluorescence-activated cell sorting (FACS) with RNA sequencing, revealed downregulation of critical inner ear development genes, including gfi1ab and atoh1a/b, which was validated by RT-qPCR. These results provide clinical and experimental evidence supporting the functional impact of the ACY1 c.1063-1G>A variant and its potential involvement in congenital hearing loss. Our findings support ACY1 as a candidate gene for hereditary hearing impairment, although additional unrelated patients and independent validation are needed to further establish the gene-disease relationship.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.","authors":"Pichao Deng, Wei Deng, Linyao Wang, Weiwu Ye, Shihong Li","doi":"10.1007/s10528-026-11415-0","DOIUrl":"https://doi.org/10.1007/s10528-026-11415-0","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, are characterized by progressive neuronal dysfunction and loss. Recent evidence highlights the importance of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, a key regulator of cellular defense mechanisms, in maintaining neuronal health and function. A narrative literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant experimental, clinical, and review studies on NRF2 signaling, physical exercise, oxidative stress, muscle-brain crosstalk, and neurodegenerative diseases. Keywords included \"NRF2\", \"Nrf2/Keap1/ARE\", \"physical exercise\", \"exercise-induced oxidative stress\", \"myokines\", \"exerkines\", \"Alzheimer's disease\", \"Parkinson's disease\", \"Huntington's disease\", and \"amyotrophic lateral sclerosis\". NRF2 modulates the expression of a variety of antioxidant and cytoprotective genes, contributing to the protection of neurons against oxidative stress, inflammation, and protein aggregation, processes central to the pathogenesis of neurodegenerative diseases. Additionally, physical activity has been identified as a powerful modulator of NRF2 activation, with exercise offering neuroprotective effects through the induction of NRF2-mediated pathways. This review explores the interplay between NRF2 activation and physical exercise in the context of neurodegenerative diseases, detailing the molecular mechanisms by which exercise influences NRF2 activity to combat cellular damage and enhance neuroprotection. We discuss the therapeutic potential of combining exercise regimens with NRF2-targeted therapies, highlighting the promise of this dual approach in slowing disease progression, improving cognitive function, and enhancing quality of life in affected individuals. Furthermore, we examine the challenges and future directions for clinical implementation, including optimal exercise protocols and the development of NRF2-based pharmacological interventions. This review underscores the importance of NRF2 as a central mediator of neuroprotection and the therapeutic promise of physical activity in the management of neurodegenerative diseases.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}