LIVIVO - Search results -

Search results

Result 1 - 10 of total 35

Search options

Article ; Online: Msi2 enhances muscle dysfunction in a myotonic dystrophy type 1 mouse model.

Sabater-Arcis, Maria / Moreno, Nerea / Sevilla, Teresa / Perez Alonso, Manuel / Bargiela, Ariadna / Artero, Ruben

2023 , Page(s) 100667

Abstract: Background: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the 3' untranslated region of the DM1 protein kinase gene. Characteristic degenerative muscle symptoms include myotonia, atrophy, and ... ...

Abstract	Background: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the 3' untranslated region of the DM1 protein kinase gene. Characteristic degenerative muscle symptoms include myotonia, atrophy, and weakness. We previously proposed an MSI2>miR-7>autophagy axis whereby MSI2 overexpression repressed miR-7 biogenesis that subsequently de-repressed muscle catabolism through excessive autophagy. Because the DM1 HSA Methods: By means of recombinant AAV murine Msi2 was overexpressed in neonates HSA Conclusions: Globally, molecular, histological, and functional data from these experiments in the HSA
Language	English
Publishing date	2023-10-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698541-X
ISSN	2320-2890 ; 2320-2890
ISSN (online)	2320-2890
ISSN	2320-2890
DOI	10.1016/j.bj.2023.100667
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Natural Compound Boldine Lessens Myotonic Dystrophy Type 1 Phenotypes in DM1 Drosophila Models, Patient-Derived Cell Lines, and HSA

Álvarez-Abril, Mari Carmen / García-Alcover, Irma / Colonques-Bellmunt, Jordi / Garijo, Raquel / Pérez-Alonso, Manuel / Artero, Rubén / López-Castel, Arturo

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Myotonic dystrophy type 1 (DM1) is a complex rare disorder characterized by progressive muscle dysfunction, involving weakness, myotonia, and wasting, but also exhibiting additional clinical signs in multiple organs and systems. Central dysregulation, ... ...

Abstract	Myotonic dystrophy type 1 (DM1) is a complex rare disorder characterized by progressive muscle dysfunction, involving weakness, myotonia, and wasting, but also exhibiting additional clinical signs in multiple organs and systems. Central dysregulation, caused by an expansion of a CTG trinucleotide repeat in the DMPK gene's 3' UTR, has led to exploring various therapeutic approaches in recent years, a few of which are currently under clinical trial. However, no effective disease-modifying treatments are available yet. In this study, we demonstrate that treatments with boldine, a natural alkaloid identified in a large-scale Drosophila-based pharmacological screening, was able to modify disease phenotypes in several DM1 models. The most significant effects include consistent reduction in nuclear RNA foci, a dynamic molecular hallmark of the disease, and noteworthy anti-myotonic activity. These results position boldine as an attractive new candidate for therapy development in DM1.
MeSH term(s)	Animals ; Mice ; Myotonic Dystrophy/drug therapy ; Myotonic Dystrophy/genetics ; Myotonic Dystrophy/metabolism ; Drosophila/genetics ; Phenotype ; Cell Line ; Trinucleotide Repeat Expansion
Chemical Substances	boldine (8I91GE2769)
Language	English
Publishing date	2023-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24129820
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Quantitative magnetic resonance imaging assessment of muscle composition in myotonic dystrophy mice.

Bargiela, Ariadna / Ten-Esteve, Amadeo / Martí-Bonmatí, Luis / Sevilla, Teresa / Perez Alonso, Manuel / Artero, Ruben

Scientific reports

2023 Volume 13, Issue 1, Page(s) 503

Abstract: Myotonic dystrophy type 1 (DM1) is a severe autosomal dominant neuromuscular disease in which the musculoskeletal system contributes substantially to overall mortality and morbidity. DM1 stems from a noncoding CTG trinucleotide repeat expansion in the ... ...

Abstract	Myotonic dystrophy type 1 (DM1) is a severe autosomal dominant neuromuscular disease in which the musculoskeletal system contributes substantially to overall mortality and morbidity. DM1 stems from a noncoding CTG trinucleotide repeat expansion in the DMPK gene. The human skeletal actin long repeat (HSA
MeSH term(s)	Humans ; Mice ; Animals ; Myotonic Dystrophy/diagnostic imaging ; Myotonic Dystrophy/genetics ; Myotonic Dystrophy/pathology ; Muscle, Skeletal/diagnostic imaging ; Muscle, Skeletal/pathology ; Trinucleotide Repeat Expansion ; Phenotype ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-01-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-27661-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: BlockmiR AONs as Site-Specific Therapeutic MBNL Modulation in Myotonic Dystrophy 2D and 3D Muscle Cells and HSA

Overby, Sarah J / Cerro-Herreros, Estefanía / Espinosa-Espinosa, Jorge / González-Martínez, Irene / Moreno, Nerea / Fernández-Costa, Juan M / Balaguer-Trias, Jordina / Ramón-Azcón, Javier / Pérez-Alonso, Manuel / Møller, Thorleif / Llamusí, Beatriz / Artero, Rubén

Pharmaceutics

2023 Volume 15, Issue 4

Abstract: The symptoms of Myotonic Dystrophy Type 1 (DM1) are multi-systemic and life-threatening. The neuromuscular disorder is rooted in a non-coding CTG microsatellite expansion in the DM1 protein kinase ( ...

Abstract	The symptoms of Myotonic Dystrophy Type 1 (DM1) are multi-systemic and life-threatening. The neuromuscular disorder is rooted in a non-coding CTG microsatellite expansion in the DM1 protein kinase (
Language	English
Publishing date	2023-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15041118
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Defined D-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease.

Rapisarda, Anna / Bargiela, Ariadna / Llamusi, Beatriz / Pont, Isabel / Estrada-Tejedor, Roger / Garcia-España, Enrique / Artero, Ruben / Perez-Alonso, Manuel

Scientific reports

2021 Volume 11, Issue 1, Page(s) 19417

Abstract: In Myotonic Dystrophy type 1 (DM1), a non-coding CTG repeats rare expansion disease; toxic double-stranded RNA hairpins sequester the RNA-binding proteins Muscleblind-like 1 and 2 (MBNL1 and 2) and trigger other DM1-related pathogenesis pathway defects. ... ...

Abstract	In Myotonic Dystrophy type 1 (DM1), a non-coding CTG repeats rare expansion disease; toxic double-stranded RNA hairpins sequester the RNA-binding proteins Muscleblind-like 1 and 2 (MBNL1 and 2) and trigger other DM1-related pathogenesis pathway defects. In this paper, we characterize four D-amino acid hexapeptides identified together with abp1, a peptide previously shown to stabilize CUG RNA in its single-stranded conformation. With the generalized sequence cpy(a/t)(q/w)e, these related peptides improved three MBNL-regulated exon inclusions in DM1-derived cells. Subsequent experiments showed that these compounds generally increased the relative expression of MBNL1 and its nuclear-cytoplasmic distribution, reduced hyperactivated autophagy, and increased the percentage of differentiated (Desmin-positive) cells in vitro. All peptides rescued atrophy of indirect flight muscles in a Drosophila model of the disease, and partially rescued muscle function according to climbing and flight tests. Investigation of their mechanism of action supports that all four compounds can bind to CUG repeats with slightly different association constant, but binding did not strongly influence the secondary structure of the toxic RNA in contrast to abp1. Finally, molecular modeling suggests a detailed view of the interactions of peptide-CUG RNA complexes useful in the chemical optimization of compounds.
MeSH term(s)	Adolescent ; Adult ; Animals ; Cells, Cultured ; Drosophila ; Female ; Fibroblasts ; Humans ; Male ; Myotonic Dystrophy/metabolism ; Peptides/metabolism ; Protein Binding ; RNA/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	MBNL1 protein, human ; Peptides ; RNA-Binding Proteins ; RNA (63231-63-0)
Language	English
Publishing date	2021-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-98866-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Proof of concept of peptide-linked blockmiR-induced MBNL functional rescue in myotonic dystrophy type 1 mouse model.

Overby, Sarah J / Cerro-Herreros, Estefanía / González-Martínez, Irene / Varela, Miguel A / Seoane-Miraz, David / Jad, Yahya / Raz, Richard / Møller, Thorleif / Pérez-Alonso, Manuel / Wood, Matthew J / Llamusí, Beatriz / Artero, Rubén

Molecular therapy. Nucleic acids

2022 Volume 27, Page(s) 1146–1155

Abstract: Myotonic dystrophy type 1 is a debilitating neuromuscular disease causing muscle weakness, myotonia, and cardiac dysfunction. The phenotypes are caused by muscleblind-like (MBNL) protein sequestration by toxic RNA in the DM1 protein kinase ( ...

Abstract	Myotonic dystrophy type 1 is a debilitating neuromuscular disease causing muscle weakness, myotonia, and cardiac dysfunction. The phenotypes are caused by muscleblind-like (MBNL) protein sequestration by toxic RNA in the DM1 protein kinase (
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2022.02.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy.

Cerro-Herreros, Estefanía / González-Martínez, Irene / Moreno-Cervera, Nerea / Overby, Sarah / Pérez-Alonso, Manuel / Llamusí, Beatriz / Artero, Rubén

Molecular therapy. Nucleic acids

2020 Volume 21, Page(s) 837–849

Abstract: Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts ...

Abstract	Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts contain 50 or more repetitions due to the sequestration of the muscleblind-like (MBNL) family of proteins. Depletion of MBNLs causes alterations in splicing patterns in transcripts that contribute to clinical symptoms such as myotonia and muscle weakness and wasting. We previously found that microRNA (miR)-23b directly regulates MBNL1 in DM1 myoblasts and mice and that antisense technology ("antagomiRs") blocking this microRNA (miRNA) boosts MBNL1 protein levels. Here, we show the therapeutic effect over time in response to administration of antagomiR-23b as a treatment in human skeletal actin long repeat (HSA
Language	English
Publishing date	2020-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2020.07.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis genes.

Cerro-Herreros, Estefania / Chakraborty, Mouli / Pérez-Alonso, Manuel / Artero, Rubén / Llamusí, Beatriz

Scientific reports

2017 Volume 7, Issue 1, Page(s) 2843

Abstract: Myotonic dystrophies (DM1-2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3'UTR of the DMPK gene and CCTG repeats in the first intron of ... ...

Abstract	Myotonic dystrophies (DM1-2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3'UTR of the DMPK gene and CCTG repeats in the first intron of the CNBP gene, respectively. Mutant RNAs containing expanded repeats are retained in the cell nucleus, where they sequester nuclear factors and cause alterations in RNA metabolism. However, for unknown reasons, DM1 is more severe than DM2. To study the differences and similarities in the pathogenesis of DM1 and DM2, we generated model flies by expressing pure expanded CUG ([250]×) or CCUG ([1100]×) repeats, respectively, and compared them with control flies expressing either 20 repeat units or GFP. We observed surprisingly severe muscle reduction and cardiac dysfunction in CCUG-expressing model flies. The muscle and cardiac tissue of both DM1 and DM2 model flies showed DM1-like phenotypes including overexpression of autophagy-related genes, RNA mis-splicing and repeat RNA aggregation in ribonuclear foci along with the Muscleblind protein. These data reveal, for the first time, that expanded non-coding CCUG repeat-RNA has similar in vivo toxicity potential as expanded CUG RNA in muscle and heart tissues and suggests that specific, as yet unknown factors, quench CCUG-repeat toxicity in DM2 patients.
MeSH term(s)	Animals ; Arrhythmias, Cardiac/etiology ; Autophagy/genetics ; DNA Repeat Expansion ; Disease Models, Animal ; Drosophila ; Gene Expression ; Locomotion ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Myotonic Dystrophy/genetics ; Myotonic Dystrophy/mortality ; Myotonic Dystrophy/physiopathology ; Myotonin-Protein Kinase/genetics ; RNA Splicing
Chemical Substances	Myotonin-Protein Kinase (EC 2.7.11.1)
Language	English
Publishing date	2017-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-02829-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models.

Cerro-Herreros, Estefania / Sabater-Arcis, Maria / Fernandez-Costa, Juan M / Moreno, Nerea / Perez-Alonso, Manuel / Llamusi, Beatriz / Artero, Ruben

Nature communications

2018 Volume 9, Issue 1, Page(s) 2482

Abstract: Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, ...

Abstract	Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs enhance MBNL protein levels and rescue pathogenic missplicing events in DM1 myoblasts. Systemic delivery of these "antagomiRs" similarly boost MBNL expression and improve DM1-like phenotypes, including splicing alterations, histopathology, and myotonia in the HSA
MeSH term(s)	3' Untranslated Regions ; Alternative Splicing ; Animals ; Cell Line ; Disease Models, Animal ; Gene Silencing ; HeLa Cells ; Humans ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Myoblasts, Skeletal/metabolism ; Myoblasts, Skeletal/pathology ; Myotonic Dystrophy/genetics ; Myotonic Dystrophy/physiopathology ; Myotonic Dystrophy/therapy ; Phenotype ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/antagonists & inhibitors ; RNA-Binding Proteins/genetics ; Up-Regulation
Chemical Substances	3' Untranslated Regions ; MBNL1 protein, human ; MBNL2 protein, human ; MIRN218 microRNA, human ; MIRN23a microRNA, human ; MicroRNAs ; RNA, Messenger ; RNA-Binding Proteins
Language	English
Publishing date	2018-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-04892-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.

Ondono, Raul / Lirio, Ángel / Elvira, Carlos / Álvarez-Marimon, Elena / Provenzano, Claudia / Cardinali, Beatrice / Pérez-Alonso, Manuel / Perálvarez-Marín, Alex / Borrell, José I / Falcone, Germana / Estrada-Tejedor, Roger

Computational and structural biotechnology journal

2020 Volume 19, Page(s) 51–61

Abstract: Myotonic Dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by toxic DMPK transcripts that carry CUG repeat expansions in the 3' untranslated region (3'UTR). The intrinsic complexity and lack of crystallographic data makes noncoding RNA ...

Abstract	Myotonic Dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by toxic DMPK transcripts that carry CUG repeat expansions in the 3' untranslated region (3'UTR). The intrinsic complexity and lack of crystallographic data makes noncoding RNA regions challenging targets to study in the field of drug discovery. In DM1, toxic transcripts tend to stall in the nuclei forming complex inclusion bodies called foci and sequester many essential alternative splicing factors such as Muscleblind-like 1 (MBNL1). Most DM1 phenotypic features stem from the reduced availability of free MBNL1 and therefore many therapeutic efforts are focused on recovering its normal activity. For that purpose, herein we present pyrido[2,3-
Language	English
Publishing date	2020-12-06
Publishing country	Netherlands
Document type	Journal Article
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2020.11.053
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED