FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3091663744> ?p ?o ?g. }

• W3091663744 abstract "In 2012 the Nobel Prize for Medicine was awarded to Sir John Gurdon and Shinya Yamanaka for their joined discovery that mature, specialized cells can be reprogrammed to become immature pluripotent cells capable of developing into all different tissues of the body. This seminal breakthrough changed our vision of developmental biology and made possible to generate in vitro from somatic cells of any healthy or affected individual Induced Pluripotent Stem Cells (iPSCs) and differentiate them into virtually all types of cells. Scientists around the world were provided with the tool of modelling human diseases, even those involving inaccessible tissues such as the nervous system, to study the pathological process. iPSCs also revealed an enormous potential for pharmaceutical and clinical applications as on these cells a myriad of small molecules or candidate drugs can be tested some of which hopefully will become new effective medicines for intractable diseases. We have generated the first iPSC-derived neuronal model for the Rubinstein-Taybi syndrome (RSTS), a mendelian neurodevelopmental disorder, characterized by facial dysmorphisms, growth and speech delay, skeletal dysplasia and intellectual disability often associated to behavior disorder. RSTS is caused by mutation in the homologous CREBBP and EP300 genes encoding proteins acting as chromatin regulators through their intertwined activity of transcriptional co-activators and acetyltransferases (KATs) on histone and non histone proteins. I summarize herein the workflow used to generate iPSC-derived neurons (iNeurons) from six RSTS patients with a variable cognitive impairment in parallel to iNeurons from four healthy controls. Immunohistochemical characterization of samples at the stages of iPSCs, neural rosettes, neural progenitors and post-mitotic cortical neurons did not reveal gross alterations in the expression of stage-specific differentiation markers across patients’ or between patients’ and controls’ neuronal cultures. Conversely, altered morphology of patients’ differentiating neurons, showing reduced branch length and increased branch number and hypoexcitability of differentiated neurons emerged as relevant “disease” biomarkers. Both the anomalous neuronal morphology and the impaired electrophysiological performance varied across iNeurons from different RSTS patients. possibly reflecting cognitive and behavioural impairment of the donor patients. To validate the identified morpho-functional markers we performed further studies on iNeurons from the RSTS patient with the most severe intellectual disability by using trichostatin A (TSA), an epidrug that by inhibiting histonedeacetylases (HDAcs), the KATs opposing enzymes, has been successfully applied in different cbp+/cbp- mouse models with improvement of some neurological abnormalities. Short acute and chronic TSA treatment of two independent neural progenitor lines from the selected RSTS patient determined in both replicas a consistent reversal of a few morphological abnormalities and a significant rescue of the defective electrophysiological performance, highlighting the potential postnatal intervention of epidrugs to ameliorate the cognitive impairment of RSTS patients." @default.
• W3091663744 created "2020-10-08" @default.
• W3091663744 creator A5088730465 @default.
• W3091663744 date "2020-09-28" @default.
• W3091663744 modified "2023-10-18" @default.
• W3091663744 title "COMPRENDERE LE BASI MOLECOLARI DELLA DISABILITÀ INTELLETTIVA ATTRAVERSO IL MODELLO DEI NEURONI DI CELLULE STAMINALI PLURIPOTENTI INDOTTE" @default.
• W3091663744 doi "https://doi.org/10.4081/scie.2019.695" @default.
• W3091663744 hasPublicationYear "2020" @default.
• W3091663744 type Work @default.
• W3091663744 sameAs 3091663744 @default.
• W3091663744 citedByCount "0" @default.
• W3091663744 crossrefType "journal-article" @default.
• W3091663744 hasAuthorship W3091663744A5088730465 @default.
• W3091663744 hasBestOaLocation W30916637441 @default.
• W3091663744 hasConcept C104317684 @default.
• W3091663744 hasConcept C107459253 @default.
• W3091663744 hasConcept C145103041 @default.
• W3091663744 hasConcept C169760540 @default.
• W3091663744 hasConcept C54355233 @default.
• W3091663744 hasConcept C551499885 @default.
• W3091663744 hasConcept C64927066 @default.
• W3091663744 hasConcept C83640560 @default.
• W3091663744 hasConcept C86803240 @default.
• W3091663744 hasConceptScore W3091663744C104317684 @default.
• W3091663744 hasConceptScore W3091663744C107459253 @default.
• W3091663744 hasConceptScore W3091663744C145103041 @default.
• W3091663744 hasConceptScore W3091663744C169760540 @default.
• W3091663744 hasConceptScore W3091663744C54355233 @default.
• W3091663744 hasConceptScore W3091663744C551499885 @default.
• W3091663744 hasConceptScore W3091663744C64927066 @default.
• W3091663744 hasConceptScore W3091663744C83640560 @default.
• W3091663744 hasConceptScore W3091663744C86803240 @default.
• W3091663744 hasLocation W30916637441 @default.
• W3091663744 hasOpenAccess W3091663744 @default.
• W3091663744 hasPrimaryLocation W30916637441 @default.
• W3091663744 hasRelatedWork W1506160043 @default.
• W3091663744 hasRelatedWork W1987822850 @default.
• W3091663744 hasRelatedWork W2000251389 @default.
• W3091663744 hasRelatedWork W2002128513 @default.
• W3091663744 hasRelatedWork W2013095276 @default.
• W3091663744 hasRelatedWork W2039193920 @default.
• W3091663744 hasRelatedWork W2247148402 @default.
• W3091663744 hasRelatedWork W3004515236 @default.
• W3091663744 hasRelatedWork W4366608843 @default.
• W3091663744 hasRelatedWork W3023895657 @default.
• W3091663744 isParatext "false" @default.
• W3091663744 isRetracted "false" @default.
• W3091663744 magId "3091663744" @default.
• W3091663744 workType "article" @default.