Neurodegeneration and cancer may share a common pathomechanism of defective cell-cycle control as a consequence of age-dependent accumulation of DNA damage. The response to DNA damage is controlled by the tumor suppressor P53 that coordinates a complex network of cellular pathways. We investigated whether the protein Tau changes the response of cells exposed to acute DNA damage . We report that Tau depletion in neuroblastoma cells severely dysregulate P53 activity and leads to reduced cell death counterbalanced by increased cell senescence. As a consequence of DNA damage, abnormal modifications of both P53 and  MDM2 were detected in Tau-KO cells suggesting an important role of Tau in the regulation of P53 modification, stability and activity . Considering the medical need with vast social implications caused by neurodegenerative tauopathies and cancer, our study may lead to innovative approaches for disease-modifying therapies.
Cells are constantly exposed to DNA damaging insults. To protect URLanism, cells developed a complex molecular response coordinated by P53 , the master regulator of DNA repair, cell division and cell fate. DNA damage accumulation and abnormal cell fate decision may represent a pathomechanism shared by aging-associated disorders such as cancer and neurodegeneration. Here, we examined this hypothesis in the context of tauopathies, a neurodegenerative disorder group characterized by Tau protein deposition. For this, the response to an acute DNA damage was studied in neuroblastoma cells with depleted Tau, as a model of loss-of-function. Under these conditions, altered P53 stability and activity result in reduced cell death and increased cell senescence. This newly discovered function of Tau involves abnormal modification of P53 and its E3 ubiquitin ligase MDM2 . Considering the medical need with vast social implications caused by neurodegeneration and cancer, our study may reform our approach to disease-modifying therapies.
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Neurodegeneration and cancer may share a common pathomechanism of defective cell-cycle control as a consequence of age-dependent accumulation of DNA damage. The response to DNA damage is controlled by the tumor suppressor
Cells are constantly exposed to DNA damaging insults. To protect URLanism, cells developed a complex molecular response coordinated by
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that coordinates a complex network of cellular pathways. We investigated whether the protein Tau changes the response of cells exposed to
, the master regulator of DNA repair, cell division and cell fate. DNA damage accumulation and abnormal cell fate decision may represent a pathomechanism shared by aging-associated disorders such as cancer and neurodegeneration. Here, we examined this hypothesis in the context of tauopathies, a neurodegenerative disorder group characterized by Tau protein deposition. For this, the response to an
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with depleted Tau, as a model of loss-of-function. Under these conditions, altered
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counterbalanced by
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As a consequence of DNA damage, abnormal modifications of both
This newly discovered function of Tau involves abnormal modification of
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its E3 ubiquitin ligase
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were detected in Tau-KO cells suggesting an important role of Tau in the regulation of P53 modification, stability and activity
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neurodegenerative tauopathies
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lead to innovative approaches for
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