A neuroprotective phase precedes striatal degeneration upon nucleolar stress

Cell Death and Differentiation
Grzegorz KreinerRosanna Parlato

Abstract

The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.

References

Jun 1, 2014·PloS One·Yuki HayashiKeiji Kimura
Oct 26, 2014·Apoptosis : an International Journal on Programmed Cell Death·Sandra NeitemeierCarsten Culmsee
Jan 19, 2016·Frontiers in Cellular Neuroscience·Rosanna Parlato, Pier G Mastroberardino
Feb 9, 2016·Neurología : publicación oficial de la Sociedad Española de Neurología·Javier RianchoJose Berciano
Jan 12, 2016·The Journal of Clinical Investigation·José R NaranjoBritt Mellström
Nov 10, 2014·Molecular Neurobiology·Anand Krishnan, Douglas W Zochodne
Jan 15, 2014·Biochimica Et Biophysica Acta·David B WangRichard S Morrison
Nov 5, 2013·Biochimica Et Biophysica Acta·Junghee LeeHoon Ryu
Nov 26, 2013·Biochimica Et Biophysica Acta·Ana PalancaMiguel Lafarga
Nov 26, 2013·Biochimica Et Biophysica Acta·Ho Tsoi, Ho Yin Edwin Chan
Jan 15, 2014·Biochimica Et Biophysica Acta·Rosanna Parlato, Birgit Liss
Oct 2, 2015·Clinical & Experimental Ophthalmology·Paul I SiaRobert J Casson
Mar 24, 2015·Frontiers in Cellular Neuroscience·Grzegorz Kreiner
Sep 20, 2016·Biochimica Et Biophysica Acta·Rui Jin, Wei Zhou
Nov 7, 2016·Apoptosis : an International Journal on Programmed Cell Death·Chunchen XiangFang Han
Jan 6, 2017·Cell Death & Disease·Marta CodrichStefano Gustincich
Apr 25, 2015·Experimental Biology and Medicine·Jason A Pfister, Santosh R D'Mello
Apr 8, 2016·Molecular & Cellular Proteomics : MCP·Lukasz P SlomnickiMichal Hetman
Aug 26, 2018·Journal of Neurochemistry·Michal Hetman, Lukasz P Slomnicki
Oct 8, 2013·Cell Death and Differentiation·J D Erickson, N G Bazan
May 23, 2019·Frontiers in Cellular Neuroscience·Astrid S Pfister
Jan 14, 2016·The Journal of Biological Chemistry·Lukasz P SlomnickiMichal Hetman
Dec 16, 2016·Molecular Neurobiology·Lukasz P SlomnickiMichal Hetman
Aug 2, 2018·Physiological Reviews·Ariel A Di NardoAlain Prochiantz
Aug 17, 2019·Cells·David P DannheisigAstrid S Pfister

Citations

Jun 26, 1998·Current Opinion in Cell Biology·F B JohnsonL Guarente
Nov 25, 2000·Human Molecular Genetics·P Hilditch-MaguireMarcy E MacDonald
Sep 8, 2001·Molecular Cell·V StambolicT W Mak
Sep 17, 2004·Journal of Neurophysiology·Gloria J Klapstein, Michael S Levine
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Oct 6, 2005·Cell Cycle·Christine Mayer, Ingrid Grummt
Mar 23, 2006·Nature Reviews. Neuroscience·Mark P Mattson, Tim Magnus
Jul 29, 2006·The Journal of Comparative Neurology·Giovanna PontiLuca Bonfanti
Aug 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jill DixonPaul A Trainor
Jan 5, 2007·BMC Neuroscience·Thomas LembergerGünther Schütz
Jul 6, 2007·Autophagy·Noboru Mizushima, Tamotsu Yoshimori
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrew D StrandKevin R Jones
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
May 20, 2008·Cell·Yi TangWei Gu
Nov 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ainhoa BilbaoRainer Spanagel
Nov 28, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rosanna ParlatoGünther Schütz
Apr 14, 2009·Biochimica Et Biophysica Acta·Robert J Ferrante
May 5, 2009·Neuroscience Letters·W Michael CaudleJing Zhang
May 5, 2009·Cell·Karen H Vousden, Carol Prives
May 13, 2009·The Journal of Biological Chemistry·Alisia CarnemollaFrancesca Persichetti
Apr 20, 2010·Nature Genetics·Andrea AlimontiPier Paolo Pandolfi
Oct 12, 2010·Brain : a Journal of Neurology·Cristina BlázquezManuel Guzmán
Oct 23, 2010·Molecular Cell·Séverine BoulonAngus I Lamond
Nov 26, 2010·The Journal of Biological Chemistry·Cynthia GomesMichal Hetman
Dec 30, 2010·Autophagy·Terje Johansen, Trond Lamark
Jan 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Claus RiekerRosanna Parlato
Jan 15, 2011·Journal of Neurovirology·Shiping ZouKurt F Hauser
Feb 8, 2011·The EMBO Journal·Takao KurodaJunn Yanagisawa
May 20, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrii DomanskyiGünther Schütz
Jul 20, 2011·The Journal of Cell Biology·Tz-Chuen JuYijuang Chern
Jul 30, 2011·PloS One·Maciej PietrzakMichal Hetman
Oct 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Alice GrisonGiannino Del Sal

Related Concepts

Striatonigral Degeneration, Infantile (Disorder)
Tumor Suppressor Genes
Abnormal Degeneration
Neostriatum
Huntington's Disease Pathway
Neurons
Neurodegenerative Disorders Pathway
Lentiform Nucleus Structure
Nerve Degeneration
FRAP1 protein, human

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