Molecular and Cellular Biology最新文献_第2页

PIH1D1 and RPAP3, Components of the PAQosome: Emerging Roles in Cellular Physiology. PAQosome的组成部分PIH1D1和RPAP3：在细胞生理学中的新作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-21 DOI: 10.1080/10985549.2025.2596726

Mahaiwon Shadang, Riyaz Ahmad Mir

引用次数: 0

From Genome Guardian to Immune Modulator: The Expanding Roles of Tumor Suppressor p53. 从基因组守护者到免疫调节剂：肿瘤抑制因子p53的扩展作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-10-23 DOI: 10.1080/10985549.2025.2571187

Weiwei Wang, Juan Liu, Zhaohui Feng, Wenwei Hu

{"title":"From Genome Guardian to Immune Modulator: The Expanding Roles of Tumor Suppressor p53.","authors":"Weiwei Wang, Juan Liu, Zhaohui Feng, Wenwei Hu","doi":"10.1080/10985549.2025.2571187","DOIUrl":"10.1080/10985549.2025.2571187","url":null,"abstract":"p53 is a key tumor suppressor, and mutations in the p53 gene occur in more than half of all human cancers. p53, which is under tight and complex regulation in cells, functions primarily as a transcription factor regulating genes involved in many cellular processes, including cell cycle arrest, apoptosis, senescence, ferroptosis, and metabolism, thereby maintaining genomic integrity and preventing tumorigenesis. While the cell-intrinsic functions of p53, which contribute to its tumor-suppressive activity, have been extensively studied, it is now clear that p53 also plays an important role in immune regulation, a connection first observed when p53 was identified as a cellular protein interacting with viral antigens. Growing evidence shows that p53 modulates both innate and adaptive immunity by regulating cytokine production, antigen presentation, and the functions of immune cells, thereby contributing to host defense against infections, inflammatory responses, and antitumor immunity. In this review, we summarize and discuss the multifaceted roles of p53 and its signaling in regulating immune functions and their implications in human diseases, particularly cancer. A better understanding of the immune-related functions of p53 is crucial for advancing cancer treatment and broadening insights into immunity and disease.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"78-95"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct Functions of the Tor1 and Tor2 Kinases in Regulation of the Ribosomal Protein Gene Expression via TORC1, Not TORC2. Tor1和Tor2激酶通过TORC1而非TORC2调控核糖体蛋白基因表达的不同功能

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1080/10985549.2025.2587084

Amala Kaja, Bhawana Uprety, Pritam Chakraborty, Sukesh R Bhaumik

{"title":"Distinct Functions of the Tor1 and Tor2 Kinases in Regulation of the Ribosomal Protein Gene Expression via TORC1, Not TORC2.","authors":"Amala Kaja, Bhawana Uprety, Pritam Chakraborty, Sukesh R Bhaumik","doi":"10.1080/10985549.2025.2587084","DOIUrl":"10.1080/10985549.2025.2587084","url":null,"abstract":"The serine/threonine kinase, TOR (target of rapamycin), exists in two complexes, namely TORC1 (with either Tor1 or Tor2 kinase) and TORC2 (that contains Tor2, but not Tor1), and its pharmacological inhibition by rapamycin impairs the PIC (pre-initiation complex) formation at the ribosomal protein genes (and hence transcription and ribosome biogenesis). However, TOR's involvement in such gene regulation has not been elucidated genetically at the level of Tor1, Tor2, TORC1 or TORC2. Here, we demonstrate that null mutation of TOR1 and short-term depletion of its expression do not affect the PIC formation (and transcription) at the ribosomal protein genes. Likewise, PIC formation and transcription are not altered in TORC2-specific tor2-tsA conditional mutant or following short-term depletion of TOR2 expression. These results support the dispensability of TORC2 for ribosomal protein gene expression, and indicate that Tor1 and Tor2 play redundant roles via TORC1 for PIC formation, and hence transcription. In agreement, the Δtor1 mutant in combination with both TORC1 and TORC2-specific tor2-tsC conditional mutation impairs PIC formation at the ribosomal protein genes with consequent reduction in transcription. Collectively, our genetic analysis support redundant, yet distinct, functions of Tor1 and Tor2 via TORC1, not TORC2, in regulation of the ribosomal protein gene expression.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"168-186"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How Particular RNA Editing Sites Can be Selectively Superior to Heterozygous SNPs Independent of Temporospatial Regulation. 特定的RNA编辑位点如何选择性地优于独立于时空调节的杂合snp。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-01-05 DOI: 10.1080/10985549.2025.2603947

Qiuhua Xie, Ling Ma, Wanzhi Cai, Hu Li, Yuange Duan

{"title":"How Particular RNA Editing Sites Can be Selectively Superior to Heterozygous SNPs Independent of Temporospatial Regulation.","authors":"Qiuhua Xie, Ling Ma, Wanzhi Cai, Hu Li, Yuange Duan","doi":"10.1080/10985549.2025.2603947","DOIUrl":"10.1080/10985549.2025.2603947","url":null,"abstract":"A-to-I RNA editing introduces A-to-G variation at post-transcriptional level, but it remains mysterious. What is the advantage of functional RNA editing compared to an A/G heterozygous SNP? Here, we provide the following situations that particular RNA editing sites can be superior to heterozygous SNPs even independent of its temporospatial regulation. (1) Assume a site with A/G heterozygote advantage. RNA editing does not undergo Mendelian segregation and recombination that inevitably produce homozygotes of lower fitness. (2) Graded RNA editing level. A snapshot of editing profile shows strong tissue-specific editing levels, providing flexible stoichiometry of edited/unedited versions, while heterozygous SNPs generally produce similar expression of two alleles. (3) Higher molecular diversity. N RNA editing sites in a gene theoretically produce a dramatic number of X = 2N mRNA haplotypes, but all SNPs in a gene can only produce two alleles. Nevertheless, we emphasize that these advantageous sites may emerge through complicated evolutionary process and remain rare across the genome. We systematically discussed the pros and cons of RNA editing versus heterozygous SNPs, deepening our understanding of the biological functions of cis-regulatory mechanisms. We provide putative answers to why evolution chose RNA editing instead of a genomic mutation at particular sites.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"238-252"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanisms of RNA Polymerase I Transcription in Health and Disease: An Overview. RNA聚合酶I转录在健康和疾病中的分子机制综述。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-23 DOI: 10.1080/10985549.2026.2628826

Bridget M Walker, Jonathan Y Chung, Haleigh G Pascual, Jyoti D Adala, Bruce A Knutson

{"title":"Molecular Mechanisms of RNA Polymerase I Transcription in Health and Disease: An Overview.","authors":"Bridget M Walker, Jonathan Y Chung, Haleigh G Pascual, Jyoti D Adala, Bruce A Knutson","doi":"10.1080/10985549.2026.2628826","DOIUrl":"10.1080/10985549.2026.2628826","url":null,"abstract":"RNA polymerase I (Pol I) is a specialized eukaryotic enzyme responsible for transcribing ribosomal DNA into precursor rRNA, a process that initiates ribosome biogenesis and supports cellular growth, metabolism, and proliferation. Recent structural and mechanistic studies have revealed unique features of Pol I architecture that enable high transcriptional output and tight regulatory control. Pol I activity is dynamically regulated by signaling pathways, epigenetic mechanisms, and chromatin structure, integrating environmental and metabolic cues to fine-tune ribosome production. Dysregulation of Pol I transcription is associated with a wide spectrum of human diseases: hyperactivation is a hallmark of cancer, whereas loss-of-function mutations cause ribosomopathies, leukodystrophies, and neurodegenerative disorders through nucleolar stress. Targeted therapies, including small-molecule inhibitors and emerging peptide-based approaches, are expanding clinical strategies to modulate Pol I activity. Beyond its canonical role, Pol I contributes to genome stability, immune regulation, and host-pathogen interactions, broadening its therapeutic relevance. This review integrates structural, mechanistic, and disease perspectives on Pol I, highlighting how fundamental discoveries are informing the next generation of targeted interventions across oncology, neurodegeneration, developmental disorders, infection, and aging.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"524-545"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation. 铜伴侣ATOX1表现出差异蛋白-蛋白相互作用，并有助于骨骼肌细胞分化。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-04 DOI: 10.1080/10985549.2026.2621941

Nathan Ferguson, Yu Zhang, Alexandra M Perez, Allison T Mezzell, Jason D Fivush, Vinit C Shanbhag, Michael J Petris, Katherine E Vest

{"title":"The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.","authors":"Nathan Ferguson, Yu Zhang, Alexandra M Perez, Allison T Mezzell, Jason D Fivush, Vinit C Shanbhag, Michael J Petris, Katherine E Vest","doi":"10.1080/10985549.2026.2621941","DOIUrl":"10.1080/10985549.2026.2621941","url":null,"abstract":"Copper is an essential but potentially toxic nutrient required for a variety of biological functions. Mammalian cells use a complex network of copper transporters and metallochaperones to maintain copper homeostasis. Previous work investigating the role of copper in various disease states has highlighted the importance of copper transporters and metallochaperones. However, questions remain about how copper distribution changes under dynamic conditions like tissue differentiation. We previously reported that the copper exporter ATP7A is required for skeletal myoblast differentiation and that its expression changes in a differentiation dependent manner. Here, we sought to further understand the ATP7A-mediated copper export pathway by examining ATOX1, the copper chaperone that delivers copper to ATP7A. To investigate the role of ATOX1 in a dynamic cellular context, we characterized its protein-protein interactions during myoblast differentiation using the proximity labeling protein APEX2 to biotinylate proteins near ATOX1. We discovered that the ATOX1 interactome undergoes dramatic changes as myoblasts differentiate. These dynamic interactions correlate with distinct phenotypes of ATOX1 deficiency in proliferating and differentiated cells. Together, our results highlight the dynamic interactome of ATOX1 and its contribution to myoblast differentiation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"391-410"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119474","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

Schizosaccharomyces pombe Telomerase RNA: Secondary Structure and Flexible-Scaffold Function. 裂糖酵母端粒酶RNA：二级结构和柔性支架功能。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-11-26 DOI: 10.1080/10985549.2025.2571189

Karen McMurdie, Allison N Peeney, Melissa A Mefford, Peter Baumann, David C Zappulla

{"title":"Schizosaccharomyces pombe Telomerase RNA: Secondary Structure and Flexible-Scaffold Function.","authors":"Karen McMurdie, Allison N Peeney, Melissa A Mefford, Peter Baumann, David C Zappulla","doi":"10.1080/10985549.2025.2571189","DOIUrl":"10.1080/10985549.2025.2571189","url":null,"abstract":"The telomerase RNA-protein enzyme is critical for most eukaryotes to complete genome copying by extending chromosome ends, thus solving the end-replication problem and postponing senescence. Despite the importance of the fission yeast Schizosaccharomyces pombe to biomedical research, very little is known about the structure of its 1212 nt telomerase RNA. We have determined the secondary structure of this large RNA, TER1, based on phylogenetics and bioinformatic modeling, as well as genetic and biochemical analyses. We find several conserved regions of the rapidly evolving TER1 RNA are important to maintain telomeres, based on testing truncation mutants in vivo, whereas many other large regions are dispensable. This is similar to budding yeast telomerase RNA, and consistent with functioning as a flexible scaffold for the RNP. We tested if the essential three-way junction works from other locations in TER1, finding that it can, supporting that it is flexibly scaffolded. Furthermore, we find that a half-sized Mini-TER1 allele, built from the catalytic core and the three-way junction, reconstitutes catalytic activity with TERT in vitro. Overall, we provide a secondary structure model for the large fission-yeast telomerase lncRNA, based on phylogenetics and molecular-genetic testing in cells, and insight into the RNP's physical and functional organization.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"96-113"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635802","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

Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells. DNA甲基化抑制剂对白血病细胞染色质组织分子和结构变化的影响。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-09-29 DOI: 10.1080/10985549.2025.2560965

Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska

{"title":"Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells.","authors":"Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska","doi":"10.1080/10985549.2025.2560965","DOIUrl":"10.1080/10985549.2025.2560965","url":null,"abstract":"DNA methylation inhibitors are widely used in treating myeloid malignancies, yet their precise effects on chromatin organization and nuclear architecture remain incompletely understood. Here, the integrated molecular, cellular, and biophysical approaches to investigate the impact of azacitidine (AZA) and decitabine (DEC) on chromatin structure and nuclear mechanics in AML-007 leukemia cells are presented. Confocal microscopy revealed drug-induced alterations in nuclear morphology and actin cytoskeleton organization, with DEC inducing significant nuclear enlargement and disorganization at lower concentrations (1.0 µM) compared to AZA (5.0 µM). Chromatin condensation assays demonstrated that DEC increased chromatin accessibility in a concentration-dependent manner, while AZA produced subtler effects. Optical tweezers measurements showed both agents reduced nuclear stiffness, with DEC exerting a greater impact. Spectroscopic analysis confirmed differential drug incorporation into DNA, with higher methylation loss and structural changes observed following DEC treatment. Refractive index mapping revealed chromatin decompaction, aligning with increased accessibility and nuclear softening. These findings demonstrate that DNA hypomethylating agents exert distinct, concentration-dependent effects on nuclear organization and chromatin structure, which can be quantified through molecular and biophysical readouts. This study underscores the value of integrative methods for revealing epigenetic drug effects on chromatin architecture in leukemia cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-Dose Caffeine Exposure Protects the Human Genome from Ionizing Radiation-Induced Damage and Prolongs Mouse Longevity. 低剂量咖啡因暴露可保护人类基因组免受电离辐射引起的损伤并延长小鼠寿命。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1080/10985549.2025.2579050

Susmita Kumari, Supriya V Vartak, Sabita Tamang, Sagar S Desai, Stuti Mukerjee, Bibha Choudary, Sathees C Raghavan

{"title":"Low-Dose Caffeine Exposure Protects the Human Genome from Ionizing Radiation-Induced Damage and Prolongs Mouse Longevity.","authors":"Susmita Kumari, Supriya V Vartak, Sabita Tamang, Sagar S Desai, Stuti Mukerjee, Bibha Choudary, Sathees C Raghavan","doi":"10.1080/10985549.2025.2579050","DOIUrl":"10.1080/10985549.2025.2579050","url":null,"abstract":"Coffee is one of the most widely consumed beverages in the world and is a rich source of caffeine, a methylxanthine. Here we show that exposure to caffeine significantly reduces ionizing radiation (IR) induced DNA breaks and resulted in no or minimal G2/M arrest within the human cell, in contrast to IR alone. At the molecular level, we demonstrate that when naked plasmid DNA or oligomeric DNA was irradiated, the number of breaks was significantly less in the presence of caffeine. The observed radioprotection was irrespective of its sequence and was due to quenching of ROS by caffeine. Besides, caffeine treatment in NOS2 knockout (KO) mice exhibited a significantly enhanced survival compared to the corresponding WT mice post-irradiation. The transcriptome analysis revealed the upregulation of the key antioxidant genes (Gpx3, Gpx7, Gpx4, Idh1, etc.) involved in playing a role in ROS homeostasis in caffeine-treated mice following exposure to IR, which was further upregulated in the NOS2 KO mice. The increase in lifespan after whole-body irradiation in mice pretreated with caffeine demonstrates the potential of caffeine-mediated radioprotection and provides compelling evidence that caffeine mitigates the detrimental effects of ionizing radiation by reducing ROS and RNS levels and enhancing the expression of antioxidant genes.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"139-167"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression. USP10在阿尔茨海默病进展中Tau病理和神经元命运中的双重调节作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1080/10985549.2025.2575950

Masahiko Takahashi, Hiroki Kitaura, Asa Nakahara, Akiyoshi Kakita, Keisuke Watanabe, Taichi Kakihana, Toshifumi Hara, Yoshinori Katsuragi, Manami Yoshita-Takahashi, Sergei Anisimov, Takayuki Abe, Masahiro Fujii

{"title":"Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression.","authors":"Masahiko Takahashi, Hiroki Kitaura, Asa Nakahara, Akiyoshi Kakita, Keisuke Watanabe, Taichi Kakihana, Toshifumi Hara, Yoshinori Katsuragi, Manami Yoshita-Takahashi, Sergei Anisimov, Takayuki Abe, Masahiro Fujii","doi":"10.1080/10985549.2025.2575950","DOIUrl":"10.1080/10985549.2025.2575950","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal cell death, brain atrophy, and cognitive decline. Aggregation of Tau protein in neurons is a critical factor in the pathogenesis of AD. Tau aggregates increase as the disease progresses and contribute to neuronal cell death. This study investigated the role of ubiquitin-specific protease 10 (USP10) in Tau pathology and neuronal viability in AD. We found that the expression of USP10 was reduced in the brains of late-stage AD patients with severe Tau aggregate accumulation, which correlated with increased neuronal apoptosis. Mechanistically, our results suggest that USP10 downregulation in late-stage AD may be due to its degradation by the accumulation of p62, an inducer of selective autophagy. Brain-specific Usp10 knockout mice show increased neuronal apoptosis during embryonic development and postnatal brain atrophy. In the P301S-Tau transgenic mice, heterozygous Usp10 knockout lowered Tau levels and slightly improved early survival, suggesting USP10 has stage-dependent effects: its reduction lessens Tau burden early but worsens neuronal loss in late stage. This study identifies USP10 as a key regulator of Tau pathology and neuronal survival in AD.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"114-137"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0