Life Science Alliance最新文献_第8页

Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons. 网状蛋白-1的合成控制损伤皮质轴突的生长和微管动力学。

IF 3.1 2区生物学

Life Science Alliance Pub Date : 2026-01-16 Print Date: 2026-04-01 DOI: 10.26508/lsa.202503571

Alejandro Luarte, Javiera Gallardo, Daniela Corvalán, Ankush Chakraborty, Cláudio Gouveia Roque, Francisca Bertin, Carlos Contreras, Juan Pablo Ramírez, André Weber, Waldo Acevedo, Werner Zuschratter, Rodrigo Herrera-Molina, Úrsula Wyneken, Andrea Paula-Lima, Tatiana Adasme-Rocha, Jorge Toledo, Rodrigo Vergara, Antonia Figueroa, Carolina González, Christian González-Billault, Ulrich Hengst, Andrés Couve

{"title":"Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons.","authors":"Alejandro Luarte, Javiera Gallardo, Daniela Corvalán, Ankush Chakraborty, Cláudio Gouveia Roque, Francisca Bertin, Carlos Contreras, Juan Pablo Ramírez, André Weber, Waldo Acevedo, Werner Zuschratter, Rodrigo Herrera-Molina, Úrsula Wyneken, Andrea Paula-Lima, Tatiana Adasme-Rocha, Jorge Toledo, Rodrigo Vergara, Antonia Figueroa, Carolina González, Christian González-Billault, Ulrich Hengst, Andrés Couve","doi":"10.26508/lsa.202503571","DOIUrl":"10.26508/lsa.202503571","url":null,"abstract":"The regenerative potential of developing cortical axons depends on intrinsic mechanisms, such as axon-autonomous protein synthesis, that are still not fully understood. An emerging factor in this regenerative response is the bidirectional interplay between microtubule dynamics and the axonal ER. We hypothesize that locally synthesized ER proteins regulate microtubule dynamics and the regeneration of cortical axons. RNA data mining identified the ER-shaping protein Reticulon-1 as a relevant candidate across eight axonal transcriptomes. Using microfluidics, we show that axonal treatment with a small RNA against Reticulon-1 mRNA (Reticulon-1 knockdown) increases outgrowth of injured cortical axons while reducing their tubulin levels. We show by live-cell imaging that axonal Reticulon-1 knockdown increases microtubule growth rate in noninjured axons and restores this parameter after injury. Axonal inhibition of the microtubule-severing protein Spastin prevents the effects of Reticulon-1 knockdown over tubulin levels and outgrowth. We provide evidence that the Reticulon-1C isoform is synthesized within axons and attenuates Spastin-mediated microtubule severing. These findings support a model in which axonal protein synthesis regulates microtubule dynamics and axon outgrowth after injury.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989891","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

Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS in Drosophila glia. 选择性自噬通过降解果蝇胶质细胞中的Su(var)2-10/PIAS调控Stat92E活性。

IF 3.1 2区生物学

Life Science Alliance Pub Date : 2026-01-07 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503375

Virág Vincze, Zsombor Esküdt, Erzsébet Fehér-Juhász, Aishwarya Sanjay Chhatre, András Jipa, Anna Rita Galambos, Dalma Feil-Börcsök, Melinda Bence, Gábor Juhász, Áron Szabó

{"title":"Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS in Drosophila glia.","authors":"Virág Vincze, Zsombor Esküdt, Erzsébet Fehér-Juhász, Aishwarya Sanjay Chhatre, András Jipa, Anna Rita Galambos, Dalma Feil-Börcsök, Melinda Bence, Gábor Juhász, Áron Szabó","doi":"10.26508/lsa.202503375","DOIUrl":"10.26508/lsa.202503375","url":null,"abstract":"Glial immunity plays a pivotal role in the maintenance of nervous system homeostasis and in responses to stress conditions, including neural injuries. The transcription factor Stat92E is activated independently of the canonical JAK/STAT pathway in Drosophila glial cells after brain injury to shape glial reactivity toward degenerating axons. However, the upstream regulatory mechanisms governing Stat92E activation remain elusive. Here, we reveal that selective autophagy gates nuclear translocation of Stat92E after injury and directs the degradation of the PIAS SUMO ligase family member Stat92E repressor, Su(var)2-10, in glia. Autophagic elimination of Su(var)2-10 mediated by its colocalization and interaction with the core autophagy factor Atg8a is required for efficient Stat92E-dependent transcription after injury. In line with this, we demonstrate that autophagy is essential for the up-regulation of an innate immune pathway in glial cells after axon injury, characterized by the induction of virus-induced RNA 1 (vir-1). We propose that autophagic Su(var)2-10 breakdown controls Stat92E activation to allow glial reactivity. These findings identify a critical role of autophagy in glial immunity as part of nervous system injury responses.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918087","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

Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium. 脑血管稳定性依赖于内皮基底外侧的pak2 -纤毛- pdgf - bb - hspgs。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2026-01-05 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503460

Shubhangi Prabhudesai, Karthikeyan Thirugnanam, Xuehong Song, Hua Yang, Mariella Errede, Francesco Girolamo, Thomas Neumann, Andrea Marzullo, Sepand Bafti, Kayla Vanderhoef, Kevin R Rarick, Andrew D Spearman, Amy Y Pan, Claudia Alvarez Alvarez, Jiyuan Yang, Fuming Zhang, Jonathan S Dordick, Daniela Virgintino, Lianchun Wang, Ramani Ramchandran

{"title":"Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium.","authors":"Shubhangi Prabhudesai, Karthikeyan Thirugnanam, Xuehong Song, Hua Yang, Mariella Errede, Francesco Girolamo, Thomas Neumann, Andrea Marzullo, Sepand Bafti, Kayla Vanderhoef, Kevin R Rarick, Andrew D Spearman, Amy Y Pan, Claudia Alvarez Alvarez, Jiyuan Yang, Fuming Zhang, Jonathan S Dordick, Daniela Virgintino, Lianchun Wang, Ramani Ramchandran","doi":"10.26508/lsa.202503460","DOIUrl":"10.26508/lsa.202503460","url":null,"abstract":"Endothelial cells (ECs) in the brain communicate with mural cells to facilitate vascular stability. Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) signaling mechanism at EC-mural cell interface helps stabilize the vasculature. How this paracrine signaling is mediated is not known. Our laboratory studies endothelial cilia, a microtubule-based organelle, and its role in promoting vascular stability. We discovered that brain endothelial cilia are located primarily on the basolateral side, and PDGF-BB is expressed in EC cilium. Thus, we hypothesized that endothelium cilium in conjunction with PDGF-BB on the basolateral side is responsible for mural cell recruitment. In this study, using a combination of zebrafish, mice, and human brain model systems, we have established a signaling paradigm wherein p21-activated kinase (PAK2) and ADP-ribosylation factor-13b (ARL13b) in ECs induce secretion of PDGF-BB. PDGF-BB associates with heparan sulfate proteoglycans (HSPGs) to form a gradient around ECs. Disrupting PAK2 affects ciliogenesis, HSPGs, and PDGF-BB gradient. We unravel a new mechanism involving endothelial cilia/PAK2-mediated PDGF-BB secretion, and retention by periendothelial HSPGs to promote vascular stability via recruiting mural cells.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12769094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906348","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

Intravital imaging of the formation and resolution of MHC class II-positive T-cell activation niches. MHCⅱ类阳性t细胞活化壁龛形成和分辨率的活体成像。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2026-01-02 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503476

David Oleksyn, Jim Miller

{"title":"Intravital imaging of the formation and resolution of MHC class II-positive T-cell activation niches.","authors":"David Oleksyn, Jim Miller","doi":"10.26508/lsa.202503476","DOIUrl":"10.26508/lsa.202503476","url":null,"abstract":"Intravital imaging has revealed many of the cellular interactions that regulate immune responses, but is limited by the number of cells that can be simultaneously identified and often restricted to analysis of a single time point. We have developed two new fluorescent reporter strains, IEbeta-mAmetrine and CD8beta-LSSmOrange, that faithfully label cells expressing MHC class II and CD8-positive conventional T cells, respectively. These fluorescent proteins are spectrally distinct from commonly used fluorescent proteins (GFP, YFP), and so, these mice can be used in combination with many previously created reporter mice. In addition, we established a protocol where we can sequentially image the same area of the ear dermis over several weeks without inducing additional inflammation. We applied these techniques to IEbeta-mAmetrine mouse co-expressing markers for CD11c, CXCL10, and CD4 T cells to quantify the formation of CXCL10-positive cell clusters, elaboration of different MHC class II-positive cells within these clusters, accumulation of CD4 T cells within these clusters, and the dissipation of these T-cell activation niches as the inflammatory response wanes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12759086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892778","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

The Janus framework of the integrated stress response: from homeostasis to maladaptation. 综合应激反应的Janus框架：从内稳态到不适应。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-29 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503523

Dogus M Altintas, Marina Cerqua, Paolo M Comoglio, Cédric Chaveroux

{"title":"The Janus framework of the integrated stress response: from homeostasis to maladaptation.","authors":"Dogus M Altintas, Marina Cerqua, Paolo M Comoglio, Cédric Chaveroux","doi":"10.26508/lsa.202503523","DOIUrl":"10.26508/lsa.202503523","url":null,"abstract":"Every cell must adapt to environmental changes. When nutrients decrease, oxygen levels fall, or protein synthesis outpaces resources, cells activate stress pathways to restore balance. Among these, the integrated stress response (ISR) stands out for its capability to integrate diverse stress signals into a unified translational output. By temporarily slowing global protein synthesis while maintaining the selective translation of stress-adaptive factors, the ISR saves energy, redirects metabolism, and promotes either recovery or, if challenges surpass repair capacity, cell death. In many chronic diseases-including cancer, metabolic, inflammatory, and fibrotic disorders-ISR activity persists. Is this persistence merely a prolonged defensive phase, or does it represent a rewired, self-sustaining state with its own control mechanisms actively reshaping cell fate and disease? We argue that chronic ISR cannot be defined by time alone, challenging the monolithic view. It signifies a qualitative shift in regulation-from rhythmic homeostasis to entrenched maladaptation. Understanding this Janus framework is essential for elucidating the origins of pathology and for guiding future fundamental and translational research.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856928","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

In vivo screen reveals specific roles of Hippo pathway components in development and regeneration. 体内筛选揭示了Hippo通路组分在发育和再生中的特定作用。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-29 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503296

Susanna E Riley, Michaela Noskova Fairley, Shijia Xia, Richard Cunningham, Justyna Cholewa-Waclaw, Yi Feng, Carsten Gram Hansen

{"title":"In vivo screen reveals specific roles of Hippo pathway components in development and regeneration.","authors":"Susanna E Riley, Michaela Noskova Fairley, Shijia Xia, Richard Cunningham, Justyna Cholewa-Waclaw, Yi Feng, Carsten Gram Hansen","doi":"10.26508/lsa.202503296","DOIUrl":"10.26508/lsa.202503296","url":null,"abstract":"The Hippo signalling pathway is a major regulator of regeneration and development. However, the comparative importance and functional roles of individual Hippo pathway components in vivo are greatly unknown, particularly within the vertebrate lineage. To gain direct and comparable insights, we took advantage of the zebrafish larva model system. We generated individual and combined CRISPR/Cas9 F0 knockouts of a range of core Hippo pathway genes, including upstream regulators, the co-transcriptional regulators Yap1/Taz, and Yap1/Taz target genes. We analysed and compared the resulting developmental and regenerative phenotypes. Our findings highlight that paralogues of core components have distinct, but in some instances overlapping, functions. Intriguingly, we find that Yap1 and Taz have differential roles during development and regeneration. In addition, we characterise and compare two tail fin regenerative paradigms: after both severe and mild injury. These injury paradigms are drastically different and elicit diverse resolution processes. We confirm critical roles of the immune system in the regenerative process. Macrophage recruitment is reduced during severe tail fin regeneration after Yap1 and Taz loss, appearing earlier in yap1 than wwtr1 Crispants and correlating with defective regenerative function. This defective macrophage involvement might therefore be one of the mediators of the deficient regeneration in these two Crispants. Overall, our analysis emphasises distinct requirements and responses of the Hippo pathway during development and across different regenerative paradigms.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856870","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

RB dependent transcriptional regulation at mitotic centromeres preserves genome stability. 有丝分裂着丝粒依赖RB的转录调控保持了基因组的稳定性。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-18 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503433

Elizabeth A Crowley, Amity L Manning

{"title":"RB dependent transcriptional regulation at mitotic centromeres preserves genome stability.","authors":"Elizabeth A Crowley, Amity L Manning","doi":"10.26508/lsa.202503433","DOIUrl":"10.26508/lsa.202503433","url":null,"abstract":"Transcripts derived from centromere repeats play a critical role in the localization and activity of kinetochore components during mitosis such that disruption of RNA polymerase II-dependent transcription compromises the fidelity of chromosome segregation. Here, we show that the retinoblastoma tumor suppressor protein (RB), a critical regulator of the G1/S cell cycle transition, additionally plays an important role in the regulation of centromere transcription during mitosis. We find that cells lacking RB experience increased RNA Polymerase II activity at mitotic centromeres and a corresponding increase in nascent RNA transcripts derived from centromere sequences. Together with high levels of centromere transcription and corresponding R-loop formation, RB-deficient cells exhibit centromere DNA breaks and local activation of ATR that correspond with increased centromere localization of Aurora B, destabilization of kinetochore-microtubule attachments, and an increase in anaphase defects. Importantly, reduction of DNA damage, ATR activity, and mitotic defects following inhibition of RNA Pol II, or targeted repression of centromere transcription through centromere tethering of Suv420h2, support that mitotic defects in RB-deficient cells are linked to centromere transcription.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781603","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

Multi-omics analysis reveals metabolic diversity underlying endothelial cell functions. 多组学分析揭示了内皮细胞功能的代谢多样性。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-17 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503526

Stephan Durot, Peter F Doubleday, Lydia Schulla, Amélie Sabine, Tatiana V Petrova, Nicola Zamboni

{"title":"Multi-omics analysis reveals metabolic diversity underlying endothelial cell functions.","authors":"Stephan Durot, Peter F Doubleday, Lydia Schulla, Amélie Sabine, Tatiana V Petrova, Nicola Zamboni","doi":"10.26508/lsa.202503526","DOIUrl":"10.26508/lsa.202503526","url":null,"abstract":"Endothelial cells (ECs) line the vascular system and are key players in vascular homeostasis, yet their metabolic diversity across tissues, vascular beds, and growth states remains poorly understood. This study examines metabolic differences between proliferating and quiescent ECs and compares blood and lymphatic endothelium using proteomics and metabolomics. Our findings indicate that metabolism in quiescent ECs is not dormant but reorganized in a cell-specific manner, with decreased heme intermediates in human umbilical vein ECs and increased branched-chain amino acid catabolism across all quiescent ECs. Consistent with the differences identified in the omics data, perturbation studies revealed that inhibiting enzymes involved in heme, glutamate, fatty acid, and nucleotide biosynthesis led to distinct phenotypic responses in blood and lymphatic ECs. These findings highlight the importance of metabolic pathways in sustaining both proliferating and quiescent ECs and reveal how ECs from different vascular beds rely on distinct metabolic processes to maintain their functional states.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774911","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

Cystatin C prevents tissue injury after lung transplantation. 胱抑素C可预防肺移植后的组织损伤。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-16 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503312

Henu Kumar Verma, Carmela Morrone, Salome Rt Rehm, Aicha Jeridi, Natalia F Smirnova, Ali Doryab, Stefanie Ai Weiß, Alexey Dashkevich, Otmar Schmid, Carlo Mümmler, Michael Gerckens, Thomas M Conlon, Matthias Hecker, Nikolaus Kneidinger, Dieter E Jenne, Ali Önder Yildirim

{"title":"Cystatin C prevents tissue injury after lung transplantation.","authors":"Henu Kumar Verma, Carmela Morrone, Salome Rt Rehm, Aicha Jeridi, Natalia F Smirnova, Ali Doryab, Stefanie Ai Weiß, Alexey Dashkevich, Otmar Schmid, Carlo Mümmler, Michael Gerckens, Thomas M Conlon, Matthias Hecker, Nikolaus Kneidinger, Dieter E Jenne, Ali Önder Yildirim","doi":"10.26508/lsa.202503312","DOIUrl":"10.26508/lsa.202503312","url":null,"abstract":"Lung transplantation (LTx) offers life-saving therapy for end-stage lung disease, yet primary graft dysfunction (PGD) and bronchiolitis obliterans syndrome remain major complications, which limit long-term outcomes. The risk of PGD increases with prolonged storage and reperfusion injury. This study investigated the protective effects of cystatin C (CysC), a cysteine protease inhibitor, against PGD, through neutralization of cathepsin B activity. LTx recipients exhibited reduced levels of CysC and greater lung damage reflected by increased γ-H2AX and ACSL4 expression, correlating with poorer outcome. Using an orthotopic LTx model, we engineered CysC-Alb, an albumin-fused, cell-permeable CysC derivative for enhanced lung preservation. Adding CysC-Alb to preservation solutions during cold storage and ex vivo lung perfusion improved oxygenation, reduced DNA damage, and minimized cell death, particularly in alveolar type 2 cells. In murine grafts, CysC-Alb decreased γ-H2AX and ACSL4 expression, markers of DNA damage and ferroptosis, respectively. These findings highlight CysC-Alb as an effective additive to mitigate early pulmonary dysfunction after LTx and improve lung graft viability and transplantation outcomes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768490","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

A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration. 胆碱能神经元生物钟在RNA代谢和介导神经变性中的作用。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-15 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503508

Sharon B Tam, Nathan J Waldeck, Matthew Wright, Jelena Mojsilovic-Petrovic, Erin M Baker, Evangelos Kiskinis, Joseph Bass, Robert G Kalb

{"title":"A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.","authors":"Sharon B Tam, Nathan J Waldeck, Matthew Wright, Jelena Mojsilovic-Petrovic, Erin M Baker, Evangelos Kiskinis, Joseph Bass, Robert G Kalb","doi":"10.26508/lsa.202503508","DOIUrl":"10.26508/lsa.202503508","url":null,"abstract":"Circadian clocks are encoded by a transcription-translation feedback loop that aligns physiological processes with the solar cycle. Previous work linking the circadian clock to the regulation of RNA-binding proteins (RBPs) provides a foundation for the vital examination of their mechanistic connections in the context of amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease commonly marked by disrupted RBP function. Here, we reveal that the spinal cord cholinergic neuron rhythmic transcriptome is enriched for genes associated with ALS and other neurodegenerative diseases. We show that there is time-of-day-dependent expression of ALS-linked RBP transcripts and rhythmic alternative splicing of genes involved in microtubule cytoskeleton organization, intracellular trafficking, and synaptic function. Through in silico analysis of RNA sequencing data from sporadic ALS patients, we find that gene expression profiles altered in disease correspond with rhythmic gene networks. Finally, we report that clock disruption through cholinergic neuron-specific deletion of clock activator BMAL1 increases neurodegeneration and drives time-of-day-dependent alternative splicing of RNA processing genes. Our results establish a role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763106","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