title: A neuroprotective role for the DNA damage checkpoint in tauopathy.
abstract: 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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Khurana
authors.forename: Paola
authors.initials: P
authors.lastname: Merlo
authors.forename: Brian
authors.initials: B
authors.lastname: DuBoff
authors.forename: Tudor A
authors.initials: TA
authors.lastname: Fulga
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Sharp
authors.forename: Shelagh D
authors.initials: SD
authors.lastname: Campbell
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.forename: Mel B
authors.initials: MB
authors.lastname: Feany
mesh_terms: D000375:Aging; D000818:Animals; D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D051379:Mice; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology