title: Brain and induced pluripotent stem cell-derived neural stem cells as an in vitro model of neurodegeneration in ataxia-telangiectasia.
abstract: The ataxia telangiectasia mutated (ATM) kinase is a key transducer of the cellular response to DNA double strand breaks and its deficiency causes ataxia-telangiectasia (A-T), a pleiotropic genetic disorder primarily characterized by cerebellar neuropathy, immunodeficiency and cancer predisposition. While enormous progress has been achieved in elucidating the biochemical and functional regulation of ATM in DNA damage response, and more recently in redox signalling and antioxidant defence, the factors that make neurons in A-T extremely vulnerable remain unclear. Given also that ATM knockout mice do not recapitulate the central nervous system phenotype, a number of human neural stem cell (hNSC) model systems have been developed to provide insights into the mechanisms of neurodegeneration associated with ATM dysfunction. Here we review the hNSC systems developed by us an others to model A-T.
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Carlessi
authors.forename: Elena
authors.initials: E
authors.lastname: Fusar Poli
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
mesh_terms: D001260:Ataxia Telangiectasia / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001921:Brain / Q000166:cytology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology*; D058953:Neural Stem Cells / Q000166:cytology*; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases