p53 prevents neurodegeneration by regulating synaptic genes.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.

Year of Publication
2014
Journal
Proc Natl Acad Sci U S A
Volume
111
Issue
50
Pages
18055-60
Date Published
2014 Dec 16
ISSN
1091-6490
URL
DOI
10.1073/pnas.1419083111
PubMed ID
25453105
PubMed Central ID
PMC4273405
Links
Grant list
P40 OD018537 / OD / NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
P40OD018537 / OD / NIH HHS / United States
Howard Hughes Medical Institute / United States
R01 GM084947 / GM / NIGMS NIH HHS / United States
R01-GM084947 / GM / NIGMS NIH HHS / United States