RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting Akt phosphorylation/activation.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Cristina MalageladaLloyd A Greene

Abstract

Previously, we reported that RTP801, a stress regulated protein, is induced in multiple cellular models of Parkinson's disease (PD), in an animal model of PD and in dopaminergic neurons of PD patients. In cellular PD models, RTP801 is both sufficient and necessary for death. We further showed that RTP801 and PD mimetics such as 6-OHDA trigger neuron death by suppressing activation of the key kinase mammalian target of rapamycin (mTOR). Here, we report that as a consequence of mTOR signaling blockade, 6-OHDA suppresses the phosphorylation and activation of Akt, a major supporter of neuron survival. This effect is mediated by RTP801 and appears to underlie neuron death induced by 6-OHDA. Examination of postmortem dopaminergic neurons reveals a consistent depletion of phospho-Akt, but not of total Akt in PD patients. These observations support a sequential mechanism in which PD-associated stresses induce RTP801, suppress mTOR signaling, deplete phosphorylated/activated Akt and permit neuron degeneration and death.

References

Jul 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L A Greene, A S Tischler
Dec 1, 1993·Neuropathology and Applied Neurobiology·S Patt, L Gerhard
Feb 21, 1997·Cell·T F FrankeL C Cantley
Nov 10, 1998·Journal of Neurology·S Fahn
Mar 9, 2002·Molecular and Cellular Biology·Tzipora ShoshaniElena Feinstein
Apr 16, 2002·Journal of Neurochemistry·Wen-Hua ZhengRémi Quirion
Jul 19, 2002·Neuron·Annette MarkusWilliam D Snider
May 9, 2003·The Journal of Biological Chemistry·Zhengqi WangClark W Distelhorst
Sep 29, 2004·Investigative Ophthalmology & Visual Science·Anat BrafmanTzipora Shoshani
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Jan 6, 2005·The Journal of Biological Chemistry·Michael N CorradettiKun-Liang Guan
Jan 15, 2005·Neurobiology of Disease·Elizabeth J RyuLloyd A Greene
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
May 19, 2005·The Journal of Biological Chemistry·Gary G Chiang, Robert T Abraham
Jul 1, 2005·Molecular and Cellular Biology·Avi SoferLeif W Ellisen
Sep 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yufeng YangBingwei Lu
Dec 13, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vikas KumarGang-Yi Wu
Dec 13, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jacek JaworskiMorgan Sheng
Sep 27, 2006·Molecular Aspects of Medicine·Barry Boland, Ralph A Nixon
Sep 29, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristina MalageladaLloyd A Greene
Nov 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Vincent RiesRobert E Burke
Oct 5, 2007·Biochimica Et Biophysica Acta·Lukasz SwiechJacek Jaworski
Nov 22, 2007·PloS One·Kathrin ThedieckMichael N Hall
Jan 17, 2008·Genes & Development·Maurice Phillip DeYoungLeif W Ellisen
Feb 26, 2008·Acta Neuropathologica·Gay RudowJuan C Troncoso

❮ Previous
Next ❯

Citations

Feb 2, 2012·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Xu-Hua GeChun-Feng Liu
Jan 24, 2009·Apoptosis : an International Journal on Programmed Cell Death·Oren A LevyLloyd A Greene
May 7, 2011·Cellular and Molecular Neurobiology·Lloyd A GreeneCristina Malagelada
Mar 5, 2013·Nature Neuroscience·Wei HuangMauro Costa-Mattioli
Jul 21, 2011·Nature Reviews. Neuroscience·Jordi BovéMiquel Vila
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hossein AleyasinDavid S Park
Aug 6, 2010·The Journal of Biological Chemistry·Sascha KarassekRaphael Stoll
Aug 22, 2013·Human Molecular Genetics·Melissa K McCoyMark R Cookson
Sep 8, 2011·Molecular and Cellular Biology·Douangsone D VadysirisackLeif W Ellisen
Feb 9, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiaotian SunOren A Levy
Jan 22, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristina MalageladaLloyd A Greene
Mar 4, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristina MalageladaLloyd A Greene
Aug 17, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiqun ChenRobert E Burke
Feb 11, 2011·Oxidative Medicine and Cellular Longevity·Zhao Zhong ChongKenneth Maiese
Sep 4, 2013·Brain : a Journal of Neurology·Heather MortiboysOliver Bandmann
Dec 10, 2013·Cell Stem Cell·Justine D MillerLorenz Studer
Nov 3, 2012·Neurochemical Research·Kangyong LiuXiaojiang Sun
Feb 5, 2016·Molecular Neurobiology·Junjun ZhaoJianliang Zhang
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Pavle MatakNancy C Andrews
Apr 15, 2015·Cellular and Molecular Neurobiology·Xiaomei WuLi Zhu
Jul 30, 2015·Neuroscience Bulletin·Dongkai GuoGuanghui Wang
Jul 11, 2013·Cell Cycle·Michael G GarelickBrian K Kennedy
Apr 17, 2015·Molecular Neurobiology·Núria Martín-FloresCristina Malagelada
Jul 11, 2014·Frontiers in Molecular Neuroscience·Nicolas DzamkoGlenda M Halliday
Oct 18, 2014·Frontiers in Cellular Neuroscience·Mercè CanalCristina Malagelada
Oct 12, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Qian ZhouLong Chen
Jun 6, 2016·Neuromolecular Medicine·Ai-Ping LanYi Hu
Aug 20, 2016·Brain : a Journal of Neurology·Yong-Hee RheeSang-Hun Lee
Sep 23, 2016·International Journal of Molecular Sciences·Syed Jafar MehdiSyed Z Imam
Oct 18, 2014·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jose L Labandeira-GarciaMaria J Guerra
Jan 31, 2017·International Journal of Molecular Sciences·Gonzalo S Tejeda, Margarita Díaz-Guerra
May 23, 2017·Toxicology Reports·Belén FernándezSabine Hilfiker
Oct 6, 2009·Neuroscience Letters·Suzanne TimmonsCora O' Neill

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Cristina MalageladaLloyd A Greene
Trends in Pharmacological Sciences
Jean-Martin BeaulieuMarc G Caron
© 2021 Meta ULC. All rights reserved