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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Ataxia Telangiectasia / pathology*
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Ataxia Telangiectasia Mutated Proteins
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Brain / cytology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Cycle Proteins / physiology
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Cells, Cultured
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DNA Damage
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Humans
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Induced Pluripotent Stem Cells / cytology*
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Induced Pluripotent Stem Cells / metabolism
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Models, Biological
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Myocardium / metabolism
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Myocardium / pathology
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Nerve Degeneration / pathology*
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Neural Stem Cells / cytology*
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Oxidation-Reduction
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor Proteins / physiology
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases