A neuroprotective role for the DNA damage checkpoint in tauopathy
Vikram Khurana
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
These authors contributed equally to this work.
Search for more papers by this authorPaola Merlo
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
These authors contributed equally to this work.
Search for more papers by this authorBrian DuBoff
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorTudor A. Fulga
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorKatherine A. Sharp
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorShelagh D. Campbell
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9
Search for more papers by this authorJürgen Götz
Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia
Search for more papers by this authorMel B. Feany
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorVikram Khurana
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
These authors contributed equally to this work.
Search for more papers by this authorPaola Merlo
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
These authors contributed equally to this work.
Search for more papers by this authorBrian DuBoff
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorTudor A. Fulga
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorKatherine A. Sharp
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorShelagh D. Campbell
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9
Search for more papers by this authorJürgen Götz
Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia
Search for more papers by this authorMel B. Feany
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Search for more papers by this authorSummary
ATM and p53, effectors of the DNA damage checkpoint, are generally considered pro-apoptotic in neurons. We show that DNA damage and checkpoint activation occurs in postmitotic neurons in animal models of tauopathy, neurodegenerative disorders that include Alzheimer’s disease. Surprisingly, checkpoint attenuation potently increases neurodegeneration through aberrant cell cycle re-entry of postmitotic neurons. These data suggest an unexpected neuroprotective role for the DNA damage checkpoint in tauopathies.
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