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dc.contributor.author
Farinelli, Mélissa
dc.contributor.author
Heitz, Fabrice D.
dc.contributor.author
Grewe, Benjamin F.
dc.contributor.author
Tyagarajan, Shiva K.
dc.contributor.author
Helmchen, Fritjof
dc.contributor.author
Mansuy, Isabelle M.
dc.date.accessioned
2018-09-20T07:54:03Z
dc.date.available
2017-06-10T02:00:13Z
dc.date.available
2018-09-20T07:54:03Z
dc.date.issued
2012-03-30
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0034047
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/50995
dc.identifier.doi
10.3929/ethz-b-000050995
dc.description.abstract
An imbalance between pro-survival and pro-death pathways in brain cells can lead to neuronal cell death and neurodegeneration. While such imbalance is known to be associated with alterations in glutamatergic and Ca2+ signaling, the underlying mechanisms remain undefined. We identified the protein Ser/Thr phosphatase protein phosphatase-1 (PP1), an enzyme associated with glutamate receptors, as a key trigger of survival pathways that can prevent neuronal death and neurodegeneration in the adult hippocampus. We show that PP1α overexpression in hippocampal neurons limits NMDA receptor overactivation and Ca2+ overload during an excitotoxic event, while PP1 inhibition favors Ca2+ overload and cell death. The protective effect of PP1 is associated with a selective dephosphorylation on a residue phosphorylated by CaMKIIα on the NMDA receptor subunit NR2B, which promotes pro-survival pathways and associated transcriptional programs. These results reveal a novel contributor to the mechanisms of neuroprotection and underscore the importance of PP1-dependent dephosphorylation in these mechanisms. They provide a new target for the development of potential therapeutic treatment of neurodegeneration.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Selective Regulation of NR2B by Protein Phosphatase-1 for the Control of the NMDA Receptor in Neuroprotection
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
7
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e34047
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02542 - Institut für Neurowissenschaften / Institute for Neuroscience::03518 - Mansuy, Isabelle / Mansuy, Isabelle
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02542 - Institut für Neurowissenschaften / Institute for Neuroscience::03518 - Mansuy, Isabelle / Mansuy, Isabelle
ethz.date.deposited
2017-06-10T02:00:33Z
ethz.source
ECIT
ethz.identifier.importid
imp59364f5f1303974319
ethz.ecitpid
pub:83223
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T08:49:41Z
ethz.rosetta.lastUpdated
2018-11-08T02:34:41Z
ethz.rosetta.versionExported
true
ethz.COinS
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