• Open Access

A neuroprotective role for the DNA damage checkpoint in tauopathy

Authors


Mel B. Feany, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 77 Louis Pasteur Ave., Room 630, Boston, MA 02115, USA. Tel.: 1 617 525 4405; fax: 1 617 525 4422; e-mail:mel_feany@hms.harvard.edu

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.

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