α-Synuclein Activates Innate Immunity but Suppresses Interferon-γ Expression in Murine Astrocytes

The European Journal of Neuroscience
Jintang WangSean X Leng

Abstract

Glial activation and neuroinflammation contribute to pathogenesis of neurodegenerative diseases, linked to neuron loss and dysfunction. α-Synuclein (α-syn), as a metabolite of neuron, can induce microglia activation to trigger innate immune response. However, whether α-syn, as well as its mutants (A53T, A30P and E46K), induces astrocyte activation and inflammatory response is not fully elucidated. In this study, we used A53T mutant and wildtype α-syns to stimulate primary astrocytes in dose- and time-dependent manners (0.5, 2, 8 and 20 μg/mL for 24 hour or 3, 12, 24 and 48 hour at 2 μg/mL), and evaluated activation of several canonical inflammatory pathway components. The results showed that A53T mutant or wildtype α-syn significantly upregulated mRNA expression of toll-like receptor (TLR)2, TLR3, nuclear factor-κB and interleukin (IL)-1β, displaying a pattern of positive dose-effect correlation or negative time-effect correlation. Such upregulation was confirmed at protein levels of TLR2 (at 20 μg/mL), TLR3 (at most doses) and IL-1β (at 3 hour) by western blotting. Blockage of TLR2 other than TLR4 inhibited TLR3 and IL-1β mRNA expressions. By contrast, interferon (IFN)-γ was significantly downregulated at mRNA, protein and pro...Continue Reading

References

Jul 4, 2001·Nature Reviews. Neuroscience·M Goedert
Apr 20, 2004·Current Topics in Developmental Biology·Erin H NorrisVirginia M-Y Lee
Apr 28, 2004·Parkinsonism & Related Disorders·Seonghan KimYoo-Hun Suh
Jun 7, 2005·Journal of Neuroinflammation·Emilie CroisierManuel B Graeber
Dec 17, 2005·Annals of Neurology·Kenya NishiokaNobutaka Hattori
Oct 3, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andis KlegerisPatrick L McGeer
Feb 6, 2007·Trends in Immunology·Cinthia FarinaEdgar Meinl
Nov 27, 2007·Journal of Neurochemistry·Ashley D ReynoldsHoward E Gendelman
Mar 20, 2009·Lancet Neurology·Etienne C Hirsch, Stéphane Hunot
May 23, 2009·Nature Reviews. Immunology·Serge Rivest
Jun 16, 2009·Neurotoxicity Research·Xiaomin SuKathleen A Maguire-Zeiss
Aug 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Paula DesplatsSeung-Jae Lee
Jan 15, 2010·The Journal of Biological Chemistry·He-Jin LeeSeung-Jae Lee
Jan 25, 2011·Neuroscience Research·Lydia Alvarez-ErvitiMatthew J A Wood
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
Jul 13, 2011·Frontiers in Neuroscience·Dawn BéraudKathleen A Maguire-Zeiss
Dec 20, 2011·Neuroscience Letters·Neda Saffarian TousiRandall L Davis
Mar 20, 2012·Journal of Neural Transmission·Brit MollenhauerMichael G Schlossmacher
Jul 4, 2012·Experimental Neurology·Melanie B WatsonMarie-Françoise Chesselet
Sep 25, 2012·Journal of Neuroimmunology·Di MaAkio Suzumura
Jun 7, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ashley S HarmsDavid G Standaert
Oct 2, 2013·Neuro-degenerative Diseases·Judith Eschbach, Karin M Danzer
Jan 29, 2014·Nature Reviews. Neurology·He-Jin LeeSeung-Jae Lee
Jan 17, 2015·Nature·Manolis Pasparakis, Peter Vandenabeele
Apr 7, 2015·PloS One·Niklas K U KoehlerElke Richartz-Salzburger
Jun 5, 2015·Frontiers in Neurology·Annamaria LanzillottaMarina Pizzi
Aug 15, 2015·The Biochemical Journal·Adelin GustotVincent Raussens

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.