Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology.

Journal of Cellular and Molecular Medicine
R LiuJ-J Pei

Abstract

Down-regulation of protein phosphatase 2A (PP2A) is thought to play a critical role in tau hyperphosphorylation in Alzheimer's disease (AD). In vitro phosphorylation of PP2A catalytic subunit at Y307 efficiently inactivates PP2A. A specific antibody against phosphorylated (p) PP2A (Y307) (PP2Ac-Yp307) was used to investigate possible PP2A down-regulation by known pathophysiological changes associated with AD, such as Abeta accumulation and oestrogen deficiency. Immunohistochemistry and immunofluorescence confocal microscopy showed an aberrant accumulation of PP2Ac-Yp307 in neurons that bear pretangles or tangles in the susceptible brain regions, such as the entorhinal cortical cortex and the hippocampus. Experimentally, increased PP2Ac-Yp307 was observed in mouse N2a neuroblastoma cells that stably express the human amyloid precursor protein with Swedish mutation (APPswe) compared with wild-type, and in the brains of transgenic APPswe/ presenilin (PS1, A246E) mice, which corresponded to the increased tau phosphorylation. Treating N2a cells with Abeta25-35 mimicked the changes of PP2Ac-Yp307 and tau phosphorylation in N2a APPswe cells. Knockout of oestrogen receptor (ER) alpha or ERbeta gave similar changes of PP2Ac-Yp307 level ...Continue Reading

References

Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A TakashimaK Imahori
Sep 1, 1993·Journal of Neurochemistry·C X GongK Iqbal
Aug 1, 1995·Seminars in Cancer Biology·D L Brautigan
Mar 14, 2000·Current Opinion in Cell Biology·D M Virshup
Mar 22, 2001·Experimental Neurology·V Vogelsberg-RagagliaV M Lee
Jan 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ling WangJan-Ake Gustafsson
Mar 8, 2003·Acta Neuropathologica·Jin-Jing PeiKhalid Iqbal
Apr 22, 2004·Journal of Neuropathology and Experimental Neurology·Estelle SontagCharles L White
Nov 13, 2004·Journal of Neuropathology and Experimental Neurology·Estelle SontagCharles L White
May 28, 2005·The American Journal of Pathology·Hitoshi TanimukaiKhalid Iqbal
Feb 24, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ke-Jie YinJin-Moo Lee
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Xiaotang FanJan-Ake Gustafsson

❮ Previous
Next ❯

Citations

Dec 18, 2012·Translational Neurodegeneration·Yale DuanZheng Zhao
Jul 2, 2014·BMC Neuroscience·Stéphanie ChasseigneauxBernadette Allinquant
Jan 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mohammad ArifKhalid Iqbal
Jul 23, 2014·Oxidative Medicine and Cellular Longevity·Regina Pessoa-PureurJoão B Rocha
Mar 28, 2008·Journal of Cellular and Molecular Medicine·J Avila
Jan 7, 2014·Expert Opinion on Therapeutic Targets·Khalid IqbalFei Liu
Jan 15, 2014·International Journal of Alzheimer's Disease·Sara H MokhtarSteven Petratos
Feb 24, 2015·Frontiers in Oncology·Kavitha RamaswamyAlex Kentsis
Mar 22, 2014·Frontiers in Molecular Neuroscience·Jean-Marie Sontag, Estelle Sontag
May 27, 2014·Frontiers in Aging Neuroscience·Meghan C McCord, Elias Aizenman
Jul 1, 2008·Neurobiology of Disease·Xin-Wen ZhouJin-Jing Pei
Sep 16, 2009·Biochimica Et Biophysica Acta·Jürgen GötzLars M Ittner
Feb 13, 2009·Journal of Cellular and Molecular Medicine·Jin-Jing Pei, Jacques Hugon
Feb 26, 2013·Environmental Toxicology·Yu SunLi-Hong Xu
Feb 16, 2019·Acta Neuropathologica Communications·Min QinXiaochuan Wang
Jun 23, 2010·Journal of Neuroscience Research·Miguel A R AmorimLuis M Garcia-Segura
Jun 22, 2018·Annual Review of Biochemistry·David L Brautigan, Shirish Shenolikar
Jun 18, 2010·CNS Neuroscience & Therapeutics·Rodrigo MedeirosFrank M LaFerla
Apr 27, 2011·Journal of Neurochemistry·Rima ObeidMarkus Herrmann
Mar 26, 2014·Neuroscience Bulletin·Moses N WainainaChunjiu Zhong
Apr 10, 2015·Neuroscience Bulletin·Yan XiongRong Liu
Oct 29, 2015·The FEBS Journal·Jaya SangodkarGoutham Narla
Oct 14, 2009·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Samanta Oliveira LoureiroRegina Pessoa-Pureur
Mar 26, 2011·Journal of Cellular and Molecular Medicine·Domenico BoscoArturo Pujia

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
electrophoresis
dot blots
transfection
confocal microscopy

Software Mentioned

Discovery Series Quantity One

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.