Open AccessA neuroprotective role for the DNA damage checkpoint in tauopathy
Author(s) -
Khurana Vikram,
Merlo Paola,
DuBoff Brian,
Fulga Tudor A.,
Sharp Katherine A.,
Campbell Shelagh D.,
Götz Jürgen,
Feany Mel B.
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00778.x
Subject(s) - g2 m dna damage checkpoint , tauopathy , neurodegeneration , biology , dna damage , neuroprotection , cell cycle checkpoint , chek1 , microbiology and biotechnology , effector , neuroscience , cell cycle , dna repair , cancer research , apoptosis , dna , disease , genetics , medicine
Summary 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.