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P53 prevents neurodegeneration by regulating synaptic genes.

ABSTRACT: DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.

SUBMITTER: Merlo P

PROVIDER: S-EPMC4273405 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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p53 prevents neurodegeneration by regulating synaptic genes.

Merlo Paola P Frost Bess B Peng Shouyong S Yang Yawei J YJ Park Peter J PJ Feany Mel M

Proceedings of the National Academy of Sciences of the United States of America 20141201 50

DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, syn ...[more]

PMID: 25453105

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p53 prevents neurodegeneration by regulating synaptic genes

Project description:DNA damage has been implicated in neurodegenerative disorders, including Alzheimer’s disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration. 4 samples: tau vs. control

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p53 prevents neurodegeneration by regulating synaptic genes

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Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration.

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| S-EPMC9292638 | biostudies-literature

Oestrogen prevents cardiomyocyte apoptosis by suppressing p38?-mediated activation of p53 and by down-regulating p53 inhibition on p38?.

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Deoxyglucose prevents neurodegeneration in culture by eliminating microglia.

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