Life Science Alliance最新文献_第10页

Nanobodies as novel tools to monitor the mitochondrial fission factor Drp1. 纳米抗体是监测线粒体裂变因子 Drp1 的新型工具。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-30 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402608

Theresa Froehlich, Andreas Jenner, Claudia Cavarischia-Rega, Funmilayo O Fagbadebo, Yannic Lurz, Desiree I Frecot, Philipp D Kaiser, Stefan Nueske, Armin M Scholz, Erik Schäffer, Ana J Garcia-Saez, Boris Macek, Ulrich Rothbauer

{"title":"Nanobodies as novel tools to monitor the mitochondrial fission factor Drp1.","authors":"Theresa Froehlich, Andreas Jenner, Claudia Cavarischia-Rega, Funmilayo O Fagbadebo, Yannic Lurz, Desiree I Frecot, Philipp D Kaiser, Stefan Nueske, Armin M Scholz, Erik Schäffer, Ana J Garcia-Saez, Boris Macek, Ulrich Rothbauer","doi":"10.26508/lsa.202402608","DOIUrl":"10.26508/lsa.202402608","url":null,"abstract":"In cells, mitochondria undergo constant fusion and fission. An essential factor for fission is the mammalian dynamin-related protein 1 (Drp1). Dysregulation of Drp1 is associated with neurodegenerative diseases including Parkinson's, cardiovascular diseases and cancer, making Drp1 a pivotal biomarker for monitoring mitochondrial status and potential pathophysiological conditions. Here, we developed nanobodies (Nbs) as versatile binding molecules for proteomics, advanced microscopy and live cell imaging of Drp1. To specifically enrich endogenous Drp1 with interacting proteins for proteomics, we functionalized high-affinity Nbs into advanced capture matrices. Furthermore, we detected Drp1 by bivalent Nbs combined with site-directed fluorophore labelling in super-resolution STORM microscopy. For real-time imaging of Drp1, we intracellularly expressed fluorescently labelled Nbs, so-called chromobodies (Cbs). To improve the signal-to-noise ratio, we further converted Cbs into a \"turnover-accelerated\" format. With these imaging probes, we visualized the dynamics of endogenous Drp1 upon compound-induced mitochondrial fission in living cells. Considering the wide range of research applications, the presented Nb toolset will open up new possibilities for advanced functional studies of Drp1 in disease-relevant models.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180355","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

PrgE: an OB-fold protein from plasmid pCF10 with striking differences to prototypical bacterial SSBs. PrgE：一种来自质粒 pCF10 的 OB-折叠蛋白，与原型细菌 SSB 有显著差异。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-29 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402693

Annika Breidenstein, Anaïs Lamy, Cyrielle Pj Bader, Wei-Sheng Sun, Paulina H Wanrooij, Ronnie P-A Berntsson

{"title":"PrgE: an OB-fold protein from plasmid pCF10 with striking differences to prototypical bacterial SSBs.","authors":"Annika Breidenstein, Anaïs Lamy, Cyrielle Pj Bader, Wei-Sheng Sun, Paulina H Wanrooij, Ronnie P-A Berntsson","doi":"10.26508/lsa.202402693","DOIUrl":"10.26508/lsa.202402693","url":null,"abstract":"A major pathway for horizontal gene transfer is the transmission of DNA from donor to recipient cells via plasmid-encoded type IV secretion systems (T4SSs). Many conjugative plasmids encode for a single-stranded DNA-binding protein (SSB) together with their T4SS. Some of these SSBs have been suggested to aid in establishing the plasmid in the recipient cell, but for many, their function remains unclear. Here, we characterize PrgE, a proposed SSB from the Enterococcus faecalis plasmid pCF10. We show that PrgE is not essential for conjugation. Structurally, it has the characteristic OB-fold of SSBs, but it has very unusual DNA-binding properties. Our DNA-bound structure shows that PrgE binds ssDNA like beads on a string supported by its N-terminal tail. In vitro studies highlight the plasticity of PrgE oligomerization and confirm the importance of the N-terminus. Unlike other SSBs, PrgE binds both double- and single-stranded DNA equally well. This shows that PrgE has a quaternary assembly and DNA-binding properties that are very different from the prototypical bacterial SSB, but also different from eukaryotic SSBs.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175489","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

Differential growth regulates asymmetric size partitioning in Caulobacter crescentus. 差异生长调节新月酵母菌的不对称大小分化

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-28 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402591

Tin Wai Ng, Nikola Ojkic, Diana Serbanescu, Shiladitya Banerjee

{"title":"Differential growth regulates asymmetric size partitioning in Caulobacter crescentus.","authors":"Tin Wai Ng, Nikola Ojkic, Diana Serbanescu, Shiladitya Banerjee","doi":"10.26508/lsa.202402591","DOIUrl":"10.26508/lsa.202402591","url":null,"abstract":"Cell size regulation has been extensively studied in symmetrically dividing cells, but the mechanisms underlying the control of size asymmetry in asymmetrically dividing bacteria remain elusive. Here, we examine the control of asymmetric division in Caulobacter crescentus, a bacterium that produces daughter cells with distinct fates and morphologies upon division. Through comprehensive analysis of multi-generational growth and shape data, we uncover a tightly regulated cell size partitioning mechanism. We find that errors in division site positioning are promptly corrected early in the division cycle through differential growth. Our analysis reveals a negative feedback between the size of daughter cell compartments and their growth rates, wherein the larger compartment grows slower to achieve a homeostatic size partitioning ratio at division. To explain these observations, we propose a mechanistic model of differential growth, in which equal amounts of growth regulators are partitioned into daughter cell compartments of unequal sizes and maintained over time via size-independent synthesis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162037","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

Metabolic adaptation pilots the differentiation of human hematopoietic cells. 人体造血细胞分化过程中的代谢适应性试点。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-27 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402747

Laëtitia Racine, Romuald Parmentier, Shreyas Niphadkar, Julie Chhun, Jean-Alain Martignoles, François Delhommeau, Sunil Laxman, Andras Paldi

{"title":"Metabolic adaptation pilots the differentiation of human hematopoietic cells.","authors":"Laëtitia Racine, Romuald Parmentier, Shreyas Niphadkar, Julie Chhun, Jean-Alain Martignoles, François Delhommeau, Sunil Laxman, Andras Paldi","doi":"10.26508/lsa.202402747","DOIUrl":"10.26508/lsa.202402747","url":null,"abstract":"A continuous supply of energy is an essential prerequisite for survival and represents the highest priority for the cell. We hypothesize that cell differentiation is a process of optimization of energy flow in a changing environment through phenotypic adaptation. The mechanistic basis of this hypothesis is provided by the established link between core energy metabolism and epigenetic covalent modifications of chromatin. This theory predicts that early metabolic perturbations impact subsequent differentiation. To test this, we induced transient metabolic perturbations in undifferentiated human hematopoietic cells using pharmacological inhibitors targeting key metabolic reactions. We recorded changes in chromatin structure and gene expression, as well as phenotypic alterations by single-cell ATAC and RNA sequencing, time-lapse microscopy, and flow cytometry. Our observations suggest that these metabolic perturbations are shortly followed by alterations in chromatin structure, leading to changes in gene expression. We also show that these transient fluctuations alter the differentiation potential of the cells.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158560","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

ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway. ERLIN1/2支架连接TMUB1和RNF170，限制胆固醇酯化，从而调节分泌途径。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-23 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402620

Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, Elena I Rugarli

{"title":"ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.","authors":"Matteo Veronese, Sebastian Kallabis, Alexander Tobias Kaczmarek, Anushka Das, Lennart Robers, Simon Schumacher, Alessia Lofrano, Susanne Brodesser, Stefan Müller, Kay Hofmann, Marcus Krüger, Elena I Rugarli","doi":"10.26508/lsa.202402620","DOIUrl":"10.26508/lsa.202402620","url":null,"abstract":"Complexes of ERLIN1 and ERLIN2 (ER lipid raft-associated 1 and 2) form large ring-like cup-shaped structures on the endoplasmic reticulum (ER) membrane and serve as platforms to bind cholesterol and E3 ubiquitin ligases, potentially defining functional nanodomains. Here, we show that ERLIN scaffolds mediate the interaction between the full-length isoform of TMUB1 (transmembrane and ubiquitin-like domain-containing 1) and RNF170 (RING finger protein 170). We identify a luminal N-terminal conserved region in TMUB1 and RNF170, which is required for this interaction. Three-dimensional modelling shows that this conserved motif binds the stomatin/prohibitin/flotillin/HflKC domain of two adjacent ERLIN subunits at different interfaces. Protein variants that preclude these interactions have been previously linked to hereditary spastic paraplegia. Using omics-based approaches in combination with phenotypic characterization of HeLa cells lacking both ERLINs, we demonstrate a role of ERLIN scaffolds in limiting cholesterol esterification, thereby favouring cholesterol transport from the ER to the Golgi apparatus and regulating Golgi morphology and the secretory pathway.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086948","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

Chemokine receptor hetero-oligomers regulate monocyte chemotaxis. 趋化因子受体异质高分子调控单核细胞趋化。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-23 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402657

Garrett A Enten, Xianlong Gao, Michelle Y McGee, McWayne Weche, Matthias Majetschak

{"title":"Chemokine receptor hetero-oligomers regulate monocyte chemotaxis.","authors":"Garrett A Enten, Xianlong Gao, Michelle Y McGee, McWayne Weche, Matthias Majetschak","doi":"10.26508/lsa.202402657","DOIUrl":"10.26508/lsa.202402657","url":null,"abstract":"It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α1-adrenoceptors (α1-ARs) through which CRs are regulated. Here, we show that arginine vasopressin receptor 1A (AVPR1A) heteromerizes with all human CRs, except chemokine (C-X-C motif) receptor (CXCR)1, in recombinant systems and that such heteromers are detectable in THP-1 cells and human monocytes. We demonstrate that ligand-free AVPR1A differentially regulates the efficacy of CR partners to mediate chemotaxis and that AVPR1A ligands disrupt AVPR1A:CR heteromers, which enhances chemokine (C-C motif) receptor (CCR)1-mediated chemotaxis and inhibits CCR2-, CCR8-, and CXCR4-mediated chemotaxis. Using bioluminescence resonance energy transfer to monitor G protein activation and CRISPR/Cas9 gene-edited THP-1 cells lacking AVPR1A or α1B-AR, we show that CRs that share the propensity to heteromerize with α1B/D-ARs and AVPR1A exist and function within interdependent hetero-oligomeric complexes through which the efficacy of CRs to mediate chemotaxis is controlled. Our findings suggest that hetero-oligomers composed of CRs, α1B/D-ARs, and AVPR1A may enable stress hormones to regulate immune cell trafficking.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086947","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 consensus molecular subtypes classification strategy for clinical colorectal cancer tissues. 临床结直肠癌组织分子亚型分类共识策略。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-23 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402730

Tim R de Back, Tan Wu, Pascale Jm Schafrat, Sanne Ten Hoorn, Miaomiao Tan, Lingli He, Sander R van Hooff, Jan Koster, Lisanne E Nijman, Geraldine R Vink, Inès J Beumer, Clara C Elbers, Kristiaan J Lenos, Dirkje W Sommeijer, Xin Wang, Louis Vermeulen

{"title":"A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues.","authors":"Tim R de Back, Tan Wu, Pascale Jm Schafrat, Sanne Ten Hoorn, Miaomiao Tan, Lingli He, Sander R van Hooff, Jan Koster, Lisanne E Nijman, Geraldine R Vink, Inès J Beumer, Clara C Elbers, Kristiaan J Lenos, Dirkje W Sommeijer, Xin Wang, Louis Vermeulen","doi":"10.26508/lsa.202402730","DOIUrl":"10.26508/lsa.202402730","url":null,"abstract":"Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the classification accuracy in two FFPE-RNA datasets with matched fresh-frozen (FF) RNA data, and an FF-derived RNA set. An FFPE-RNA application cohort of metastatic CRC patients was established, partly treated with anti-EGFR therapy. Key characteristics per CMS were assessed. Cross-referenced with matched benchmark FF CMS calls, the CMSFFPE classifier strongly improved classification accuracy in two FFPE datasets compared with the original CMSClassifier (63.6% versus 40.9% and 83.3% versus 66.7%, respectively). We recovered CMS-specific recurrence-free survival patterns (CMS4 versus CMS2: hazard ratio 1.75, 95% CI 1.24-2.46). Key molecular and clinical associations of the CMSs were confirmed. In particular, we demonstrated the predictive value of CMS2 and CMS3 for anti-EGFR therapy response (CMS2&3: odds ratio 5.48, 95% CI 1.10-27.27). The CMSFFPE classifier is an optimized FFPE-curated research tool for CMS classification of clinical CRC samples.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086768","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 multiomic characterization of the leukemia cell line REH using short- and long-read sequencing. 利用长短线程测序对白血病细胞系 REH 进行多组学特征描述。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-22 Print Date: 2024-08-01 DOI: 10.26508/lsa.202302481

Mariya Lysenkova Wiklander, Gustav Arvidsson, Ignas Bunikis, Anders Lundmark, Amanda Raine, Yanara Marincevic-Zuniga, Henrik Gezelius, Anna Bremer, Lars Feuk, Adam Ameur, Jessica Nordlund

{"title":"A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing.","authors":"Mariya Lysenkova Wiklander, Gustav Arvidsson, Ignas Bunikis, Anders Lundmark, Amanda Raine, Yanara Marincevic-Zuniga, Henrik Gezelius, Anna Bremer, Lars Feuk, Adam Ameur, Jessica Nordlund","doi":"10.26508/lsa.202302481","DOIUrl":"10.26508/lsa.202302481","url":null,"abstract":"The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) ETV6::RUNX1 translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-yr-old at relapse, the cell line offers a practical model for the study of pediatric B-ALL. In recent years, short- and long-read DNA and RNA sequencing have emerged as a complement to karyotyping techniques in the resolution of structural variants in an oncological context. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole-genome sequencing, IsoSeq RNA sequencing, and short-read Illumina sequencing to create a detailed genomic and transcriptomic characterization of the REH cell line. Whole-genome sequencing clarified the molecular traits of disrupted ALL-associated genes including CDKN2A, PAX5, BTG1, VPREB1, and TBL1XR1, as well as the glucocorticoid receptor NR3C1 Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081886","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

Novel variants in TECRL leading to catecholaminergic polymorphic ventricular tachycardia. 导致儿茶酚胺能多态性室性心动过速的 TECRL 新变异。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-22 Print Date: 2024-08-01 DOI: 10.26508/lsa.202402572

Douglas Jones, Jacob Hartung, Elizabeth Lasalle, Alejandro Borquez, Viridiana Murillo, Lucia Guidugli, Kiely N James, Stephen F Kingsmore, Nicole G Coufal

引用次数: 0

Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS. 甘醇酸和D-乳酸--DJ-1的潜在产物--可恢复FUS-ALS和SOD1-ALS的神经退行性变。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-05-17 Print Date: 2024-08-01 DOI: 10.26508/lsa.202302535

Arun Pal, Dajana Grossmann, Hannes Glaß, Vitaly Zimyanin, René Günther, Marica Catinozzi, Tobias M Boeckers, Jared Sterneckert, Erik Storkebaum, Susanne Petri, Florian Wegner, Stephan W Grill, Francisco Pan-Montojo, Andreas Hermann

{"title":"Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.","authors":"Arun Pal, Dajana Grossmann, Hannes Glaß, Vitaly Zimyanin, René Günther, Marica Catinozzi, Tobias M Boeckers, Jared Sterneckert, Erik Storkebaum, Susanne Petri, Florian Wegner, Stephan W Grill, Francisco Pan-Montojo, Andreas Hermann","doi":"10.26508/lsa.202302535","DOIUrl":"10.26508/lsa.202302535","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes of mitochondria and lysosomes in FUS- and SOD1-ALS patient-derived motoneurons (MNs). This was not only accompanied by restoration of mitochondrial membrane potential but even dependent on it. Despite presenting an axonal transport deficiency as well, TDP43 patient-derived MNs did not share mitochondrial depolarization and did not respond to GA/DL treatment. GA and DL also restored cytoplasmic mislocalization of FUS and FUS recruitment to DNA damage sites, recently reported being upstream of the mitochondrial phenotypes in FUS-ALS. Whereas these data point towards the necessity of individualized (gene-) specific therapy stratification, it also suggests common therapeutic targets across different neurodegenerative diseases characterized by mitochondrial depolarization.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958253","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