Search results for "Atròfia muscular"

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Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes

2018

Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5′ splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformati…

0301 basic medicineIndolesCOMPOUND LIBRARIESDrug Evaluation PreclinicalGeneral Physics and AstronomyBiotecnologiaAnimals Genetically ModifiedExonMolecular Targeted TherapyRegulatory Elements Transcriptionallcsh:ScienceHUMAN-DISEASE GENESBIOACTIVE SMALL MOLECULESMultidisciplinaryChemistryDrug discovery[CHIM.ORGA]Chemical Sciences/Organic chemistryQImidazolesMUTATION PATTERNExonsSMA*3. Good healthCell biologySurvival of Motor Neuron 2 ProteinPhenotypeCribratgeRNA splicingNUCLEOTIDE STRUCTUREDrosophilaMESSENGER-RNACOMPUTATIONAL TOOLSMedical screeningMYOTONIC-DYSTROPHYScienceMuscular atrophyArticleGeneral Biochemistry Genetics and Molecular BiologyGenètica molecularMuscular Atrophy Spinal03 medical and health sciencesddc:570SPLICING MODIFIERSmedicineAnimalsHumansHIV-1 TARRNA MessengerAtròfia muscularMessenger RNAAlternative splicingRNAGeneral ChemistrySpinal muscular atrophymedicine.diseaseAlternative Splicing030104 developmental biologyRNAlcsh:QRNA Splice SitesHeLa CellsNature Communications
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Consenso Delphi de las recomendaciones para el tratamiento de los pacientes con atrofia muscular espinal en España (consenso RET-AME)

2021

Resumen Introduccion La atrofia muscular espinal (AME) es una enfermedad neurodegenerativa, causada por una mutacion bialelica del gen 5q SMN1, que afecta predominantemente a las neuronas motoras del asta anterior medular causando una progresiva debilidad y atrofia muscular. La aparicion de tratamientos modificadores del curso de la enfermedad esta cambiando considerablemente la historia natural de la AME, pero existe todavia incertidumbre sobre que pacientes se pueden beneficiar de estos tratamientos y como se deberia medir ese beneficio. Metodologia Un grupo de expertos especialistas en neurologia, neuropediatria y rehabilitacion, y de la asociacion de pacientes con AME de Espana, analiza…

GeneticsMuscular atrophyNeurology (clinical)Atròfia muscularGenèticaNeurología
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