Exogenous α-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes

BMC Neuroscience
Emmy H RannikkoPhilipp J Kahle

Abstract

The pathological hallmarks of Parkinson's disease are intracellular inclusions composed mainly of misfolded α-synuclein (αSYN). Under physiological conditions αSYN is mostly localized in synapses. In addition, a portion of αSYN is secreted to the extracellular space, where it may be sequestered by neighboring cells and could induce inflammatory responses. The mechanisms of αSYN internalization and signal transduction are not unequivocally clarified. In this work we investigated in primary mouse astrocytes the involvement of toll-like receptor 4 (TLR4) in the induction of inflammatory responses upon exposure to purified human αSYN produced in bacteria. The mRNA induction of pro-inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase-2 was significantly reduced in TLR4 knockout astrocytes. The αSYN-mediated activation of c-Jun N-terminal kinases and p38 mitogen-activated protein kinase tended to be diminished, and nuclear translocation of the p65 subunit of nuclear factor κB was abolished in TLR4 knockout astrocytes. In contrast, the uptake of exogenous αSYN was unaffected by TLR4 knockout. Extracellular αSYN can activate pro-inflammatory TLR4 pathways in astrocytes, whereas αSYN uptake is independent of TLR4.

References

Jan 1, 1985·Methods in Enzymology·B Hamprecht, F Löffler
Jan 1, 1993·Neuroscience·P DamierF Javoy-Agid
Aug 28, 1997·Nature·M G SpillantiniM Goedert
May 23, 1998·The Journal of Biological Chemistry·W S DavidsonJ M George
Aug 1, 2000·The Journal of Biological Chemistry·E JoP E Fraser
Jan 29, 2002·Nature Cell Biology·Hideo FujiwaraTakeshi Iwatsubo
Feb 28, 2002·Trends in Immunology·Mihai G NeteaJos W M Van der Meer
Oct 16, 2002·The Journal of Biological Chemistry·Masato HasegawaTakeshi Iwatsubo
Jan 22, 2003·Acta Neuropathologica·Seishi TeradaShigetoshi Kuroda
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Jul 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Doris L FortinRobert H Edwards
Mar 26, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei ZhangJing Zhang
Jun 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·He-Jin LeeSeung-Jae Lee
Sep 30, 2005·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·O YokotaS Kuroda
Dec 15, 2006·Neurobiology of Aging·Andis KlegerisPatrick L McGeer
Jun 1, 2007·Neurobiology of Aging·Xiaomin SuHoward J Federoff
Sep 14, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Nadia StefanovaGregor K Wenning
Jan 10, 2008·Neuro-degenerative Diseases·Robin BarbourTamie J Chilcote
Feb 23, 2008·The International Journal of Biochemistry & Cell Biology·He-Jin LeeSeung-Jae Lee
May 22, 2008·Biochemical and Biophysical Research Communications·He-Jin LeeSeung-Jae Lee
Dec 24, 2008·The Journal of Clinical Investigation·Vanessa BrochardStéphane Hunot
Mar 20, 2009·Lancet Neurology·Etienne C Hirsch, Stéphane Hunot
Nov 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kelvin C LukVirginia M-Y Lee
Jan 15, 2010·The Journal of Biological Chemistry·He-Jin LeeSeung-Jae Lee
Mar 23, 2010·Cell·Christopher K GlassFred H Gage
Jul 23, 2011·PloS One·Evangelia EmmanouilidouKostas Vekrellis
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Leonidas Stefanis
Jul 25, 2012·Cell Death & Disease·O Marques, T F Outeiro
Mar 26, 2013·Neurochemical Research·Tomasz BrudekBente Pakkenberg
Apr 20, 2014·Experimental & Molecular Medicine·Changyoun KimSeung-Jae Lee

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Citations

May 21, 2018·The European Journal of Neuroscience·Jintang WangSean X Leng
Dec 8, 2017·Cell Biology and Toxicology·Wenbo YuBaoguo Xiao
Jan 15, 2019·Cellular and Molecular Neurobiology·Alice FilippiniIsabella Russo
Apr 21, 2019·Journal of Neurochemistry·Amir Tayaranian MarvianTiago Fleming Outeiro
Nov 11, 2016·Nature·Asa Abeliovich, Aaron D Gitler
Aug 11, 2016·The Journal of Physiology·Arik TzourAlexander M Binshtok
Oct 4, 2019·Expert Opinion on Therapeutic Targets·Gunnar R LeitnerAndis Klegeris
Sep 1, 2019·Current Alzheimer Research·Laura Trujillo-EstradaFrank M LaFerla
Jul 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bruna T DiasAna Paula C A Lima
Jun 30, 2018·International Journal of Molecular Medicine·Wangshu DaiXiaoning Zeng
Mar 1, 2017·Frontiers in Neurology·Carmen D RietdijkAletta D Kraneveld
Apr 25, 2019·Cellular and Molecular Life Sciences : CMLS·Minna OksanenJari Koistinaho
Jul 7, 2017·Frontiers in Cellular and Infection Microbiology·Wen HeJing Ye
Feb 13, 2019·International Journal of Molecular Sciences·Michiel Van BulckJose A Morales-Garcia
Feb 25, 2019·Acta Neuropathologica·Zachary A SorrentinoParamita Chakrabarty
May 22, 2019·Acta Neuropathologica Communications·Zuzana KrejciovaStanley B Prusiner
Nov 30, 2019·Frontiers in Molecular Neuroscience·Cameron WellsNitin K Saksena
Nov 15, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Romina VuonoJanelle Drouin-Ouellet
Apr 23, 2019·Journal of Neurochemistry·Luan Pereira DinizFlávia Carvalho Alcantara Gomes
Dec 14, 2019·Journal of Neuroinflammation·Yuanyuan LiJun Liu
Sep 26, 2020·Experimental & Molecular Medicine·Rachael H Earls, Jae-Kyung Lee
Apr 4, 2019·Frontiers in Aging Neuroscience·Isadora MatiasFlávia Carvalho Alcantara Gomes
Dec 15, 2018·Glia·Qiao-Qiao Yang, Jia-Wei Zhou
Jul 3, 2019·Frontiers in Cellular Neuroscience·Violetta Refolo, Nadia Stefanova
Aug 13, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Imola WilhelmIstván A Krizbai
Oct 2, 2019·Frontiers in Molecular Neuroscience·Qian-Qian ChenJia-Yi Li
Dec 3, 2020·Frontiers in Cell and Developmental Biology·Yu-Mi JeonHyung-Jun Kim
Dec 1, 2017·Molecular and Cellular Neurosciences·Wen-Wen YuDan Zhang

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Methods Mentioned

BETA
nuclear
PCR
nuclear translocation
transgenic
dot blots
protein assay
electrophoresis

Software Mentioned

ExPASy
ImageJ
AxioVision
StatView
JMP
ProtParam

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