mTor mediates tau localization and secretion: Implication for Alzheimer's disease

Biochimica Et Biophysica Acta
Zhi TangJin-Jing Pei

Abstract

Abnormally hyperphosphorylated tau aggregates form paired helical filaments (PHFs) in neurofibrillary tangles, a key hallmark of Alzheimer's disease (AD) and other tauopathies. The cerebrospinal fluid (CSF) levels of soluble total tau and phospho-tau from clinically diagnosed AD patients are significantly higher compared with controls. Data from both in vitro and in vivo AD models have implied that an aberrant increase of mammalian target of rapamycin (mTor) signaling may be a causative factor for the formation of abnormally hyperphosphorylated tau. In the present study, we showed that in post-mortem human AD brain, tau was localized within different organelles (autophagic vacuoles, endoplasmic reticulum, Golgi complexes, and mitochondria). In human SH-SY5Y neuroblastoma cells stably carrying different genetic variants of mTor, we found a common link between the synthesis and distribution of intracellular tau. mTor overexpression or the lack of its expression was responsible for the altered balance of phosphorylated (p-)/-non phosphorylated (Np-) tau in the cytoplasm and different cellular compartments, which might facilitate tau deposition. Up-regulated mTor activity resulted in a significant increase in the amount of cytosoli...Continue Reading

References

Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Nov 1, 1989·Neurobiology of Aging·W BondareffD L Hauser
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·I Grundke-IqbalL I Binder
May 1, 1973·The Journal of Cell Biology·K T Tokuyasu
Feb 17, 1995·Neuroscience Letters·M JensenL Lannfelt
Jul 1, 1997·Neurobiology of Aging·W SilvermanJ Wegiel
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P GreenfieldH Xu
Sep 28, 1999·Journal of Neuropathology and Experimental Neurology·J J PeiR F Cowburn
Jan 7, 2000·The American Journal of Pathology·G K GourasN R Relkin
Dec 2, 2000·Science·D J Klionsky, S D Emr
Jun 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·A AlonsoK Iqbal
Nov 5, 2002·The American Journal of Pathology·Reisuke H TakahashiGunnar K Gouras
Jun 1, 2004·Journal of Cell Science·Yukiko KabeyaTamotsu Yoshimori
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Benoit FevrierGraça Raposo
Oct 6, 2005·The Journal of Cell Biology·W Haung YuRalph A Nixon
Dec 21, 2005·FEBS Letters·Jin-Jing PeiBengt Winblad
Feb 1, 2006·Molecular and Cellular Neurosciences·J FauréR Sadoul
Jul 29, 2006·Autophagy·Ana Maria CuervoAlexei Terman
Aug 18, 2006·FEBS Letters·Alberto Gómez-RamosJesús Avila
Sep 9, 2006·Cell Motility and the Cytoskeleton·Carole Abi FarahNicole Leclerc
Jul 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry BolandRalph A Nixon
Aug 2, 2008·Autophagy·Sandra Díaz-TroyaJosé L Crespo
Aug 22, 2008·Neurobiology of Aging·Evangelia EmmanouilidouKostas Vekrellis
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Camilla A Hansson PetersenMaria Ankarcrona
Feb 3, 2009·Acta Neuropathologica·Khalid IqbalInge Grundke-Iqbal
Feb 13, 2009·Journal of Cellular and Molecular Medicine·Jin-Jing Pei, Jacques Hugon
Mar 14, 2009·The Journal of Biological Chemistry·Bess FrostMarc I Diamond
Apr 28, 2009·Autophagy·Daijun Ling, Paul M Salvaterra
Feb 25, 2010·The Journal of Biological Chemistry·Antonella CaccamoSalvatore Oddo

❮ Previous
Next ❯

Citations

Jan 12, 2016·Biomolecules·Mahmoud Bukar MainaLouise C Serpell
Dec 24, 2015·Frontiers in Cellular Neuroscience·Marcos J Guerrero-MuñozDiana L Castillo-Carranza
Oct 7, 2015·Frontiers in Neuroscience·Gunjan JoshiYanzhuang Wang
Oct 4, 2016·Expert Review of Neurotherapeutics·Antonella TramutolaFabio Di Domenico
Dec 8, 2015·Biochimica Et Biophysica Acta·Veronica Galvan, Matthew J Hart
Feb 13, 2017·Progress in Neurobiology·Rafael FrancoMarta Zamarbide
Feb 6, 2017·Journal of Alzheimer's Disease : JAD·Lucia BuccarelloTiziana Borsello
Mar 23, 2018·Journal of Medicinal Food·Alice Barros CâmaraRodrigo Juliani Siqueira Dalmolin
May 8, 2018·Cells·Athanasios MetaxakisNektarios Tavernarakis
Apr 28, 2018·The Journal of Biological Chemistry·Basant A AbdulrahmanHermann M Schatzl
Feb 14, 2016·Cytoskeleton·James R Bamburg, Barbara W Bernstein
Dec 14, 2019·Brain : a Journal of Neurology·Sarah GourmaudDelia M Talos
Feb 28, 2020·Clinical Interventions in Aging·Qingqing YinXunyao Hou
Nov 2, 2019·Cellular and Molecular Life Sciences : CMLS·Cecilia A BrunelloHenri J Huttunen
Sep 22, 2017·Diseases·Bodo C Melnik, Gerd Schmitz
Dec 1, 2018·Acta Neuropathologica Communications·Simon DujardinLuc Buée
Sep 16, 2017·Frontiers in Molecular Neuroscience·Federica CiregiaGiuseppe Palmisano
Feb 15, 2018·Frontiers in Aging Neuroscience·Md Sahab UddinAdrian M Stankiewicz
Sep 5, 2017·Journal of Alzheimer's Disease : JAD·Monica JavidniaCharbel E-H Moussa
Dec 12, 2018·Frontiers in Physiology·Rosanna SalviaPatrizia Falabella
Oct 15, 2015·Npj Aging and Mechanisms of Disease·Joshua S TalboomSalvatore Oddo
Aug 4, 2020·Frontiers in Neuroscience·Arti TyagiNitesh Kumar Poddar
Mar 20, 2020·International Journal of Molecular Sciences·Gyeong Joon MoonSang Ryong Kim
Oct 20, 2020·Frontiers in Molecular Neuroscience·Maria MerezhkoHenri J Huttunen
Jun 27, 2019·Progress in Neurobiology·Thomas W RöslerGünter U Höglinger
Feb 18, 2020·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Mehmet OzansoyUlkan Kilic
Aug 14, 2020·International Journal of Biological Macromolecules·Shibi MuralidarBalamurugan Palaniappan
May 29, 2021·The Biochemical Journal·Dhasarathan Ganesan, Qian Cai
Jun 16, 2021·Communications Biology·Carlos G SanchezFiona Elwood
Jul 25, 2021·International Journal of Molecular Sciences·Tadanori HamanoYasunari Nakamoto
May 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Lenka HromadkovaSaak V Ovsepian
Sep 27, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elodie LerouxMorvane Colin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

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.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

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.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

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: Endosomes

Dysfunctional endosomal trafficking may be associated with Alzheimer’s disease (AD) pathology. Targeting the endosome may advance treatment options for AD. Here is the latest research on endosomes and AD.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.