Intracellular amyloid beta expression leads to dysregulation of the mitogen-activated protein kinase and bone morphogenetic protein-2 signaling axis.

PloS One
Eric CruzSurinder K Batra

Abstract

Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by the parenchymal accumulation of extracellular amyloid beta plaques. However, recent findings suggest intraneuronal amyloid beta (iAβ1-42) accumulation precedes extracellular deposition. Furthermore, the pathologic increase in iAβ1-42 has been implicated in dysregulation of cellular mechanisms critically important in axonal transport. Owing to neuronal cell polarity, retrograde and anterograde axonal transport are essential trafficking mechanism necessary to convey membrane bound neurotransmitters, neurotrophins, and endosomes between soma and synaptic interfaces. Although iAβ1-42 disruption of axonal transport has been implicated in dysregulation of neuronal synaptic transmission, the role of iAβ1-42 and its influence on signal transduction involving the mitogen-activated protein kinase (MAPK) and morphogenetic signaling axis are unknown. Our biochemical characterization of intracellular amyloid beta accumulation on MAPK and morphogenetic signaling have revealed increased iAβ1-42 expression leads to significant reduction in ERK 1/2 phosphorylation and increased bone morphogenetic protein 2 dependent Smad 1/5/8 phosphorylation. Furthermore, rescue o...Continue Reading

References

Sep 1, 1996·Brain & Development·E C YuenW C Mobley
Sep 28, 1999·Journal of Neuropathology and Experimental Neurology·J J PeiR F Cowburn
Mar 27, 2001·Muscle & Nerve·A Eisen, M Weber
Sep 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Simona CapsoniAntonino Cattaneo
Feb 26, 2005·Science·Gorazd B StokinLawrence S B Goldstein
Oct 15, 2005·Nature Reviews. Neuroscience·Michael Coleman
Nov 25, 2005·Journal of Neurology, Neurosurgery, and Psychiatry·L A van de PolP Scheltens
Aug 31, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Lawrence K Low, Hwai-Jong Cheng
Sep 16, 2006·The Journal of Biological Chemistry·Christopher G EvansJason E Gestwicki
Dec 30, 2006·Nature Reviews. Neuroscience·John A AllenMark M Rasenick
Jun 7, 2007·Nature Reviews. Neuroscience·Frank M LaFerlaSalvatore Oddo
Nov 7, 2008·Expert Review of Neurotherapeutics·Elliott J MufsonStephen D Ginsberg
Apr 5, 2011·Chemical Biology & Drug Design·Ashley A Reinke, Jason E Gestwicki
Mar 27, 2012·Trends in Cell Biology·Maria AscanoRejji Kuruvilla
Sep 1, 2012·Nature Protocols·Gerard M J BeaudoinJyothi Arikkath
Jan 31, 2013·Nature Reviews. Neuroscience·Stéphanie Millecamps, Jean-Pierre Julien
Nov 13, 2013·The Journal of Cell Biology·Martijn P J DekkersYves-Alain Barde
Feb 5, 2014·Cold Spring Harbor Perspectives in Biology·Katharina E Cosker, Rosalind A Segal
Sep 19, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristian RipoliClaudio Grassi
Aug 30, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·UNKNOWN Alzheimer's Association

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Citations

Jun 4, 2020·Omics : a Journal of Integrative Biology·Sayali Chandrashekhar DeolankarThottethodi Subrahmanya Keshava Prasad
Jan 16, 2019·International Journal of Molecular Sciences·Teresa JanasTadeusz Janas
Nov 17, 2020·Frontiers in Aging Neuroscience·Natalia SalvadoresFelipe A Court

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Methods Mentioned

BETA
Genotyping
transfection
flow cytometry

Software Mentioned

BD FACSDiva
MedCalc
SigmaPlot
LI
COR Image Studio Lite

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