title: ATM-deficient human neural stem cells as an in vitro model system to study neurodegeneration.
abstract: Loss of ATM kinase, a transducer of the DNA damage response and redox sensor, causes the neurodegenerative disorder ataxia-telangiectasia (A-T). While a great deal of progress has been made in elucidating the ATM-dependent DNA damage response (DDR) network, a key challenge remains in understanding the selective susceptibility of the nervous system to faulty DDR. Several factors appear implicated in the neurodegenerative phenotype in A-T, but which of them plays a crucial role remains unclear, especially since mouse models of A-T do not fully mirror the respective human syndrome. Therefore, a number of human neural stem cell (hNSC) systems have been developed to get an insight into the molecular mechanisms of neurodegeneration as consequence of ATM inactivation. 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: Lidia
authors.initials: L
authors.lastname: De Filippis
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D009420:Nervous System / Q000166:cytology / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; DNA damage response; Hypoxia; Neural stem cells; Neurodegeneration; iPS cells