Pathomechanism characterization and potential therapeutics identification for SCA3 targeting neuroinflammation.

Aging
Ya-Jen ChiuChiung-Mei Chen

Abstract

Polyglutamine (polyQ)-mediated spinocerebellar ataxias (SCA) are caused by mutant genes with expanded CAG repeats encoding polyQ tracts. The misfolding and aggregation of polyQ proteins result in increased reactive oxygen species (ROS) and cellular toxicity. Inflammation is a common manifestation of oxidative stress and inflammatory process further reduces cellular antioxidant capacity. Increase of activated microglia in the pons of SCA type 3 (SCA3) patients suggests the involvement of neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of indole compound NC009-1, 4-aminophenol-arachidonic acid derivative AM404, quinoline compound VB-037 and chalcone-coumarin derivative LM-031 using human HMC3 microglia and SCA3 ATXN3/Q75-GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing NO, IL-1β, TNF-α and IL-6 production and CD68 expression of IFN-γ-activated HMC3 microglia. In retinoic acid-differentiated ATXN3/Q75-GFP SH-SY5Y cells inflamed with IFN-γ-primed HMC3 conditioned medium, treatment with the tested compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced polyQ aggregation and ROS and/or pr...Continue Reading

References

Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·P KovarikT Decker
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yaohui ChaiHenry L Paulson
Sep 26, 2002·The Journal of Biological Chemistry·Fusheng LiDebabrata Chakravarti
Apr 22, 2004·Lancet Neurology·Ludger SchölsOlaf Riess
May 18, 2005·The Cerebellum·Mario-Ubaldo Manto
Aug 12, 2005·Journal of Biomolecular Screening·Richik N GhoshRobert H Oakley
Sep 24, 2005·Current Topics in Medicinal Chemistry·David M Goldstein, Tobias Gabriel
Dec 21, 2005·The Journal of Cell Biology·Ji-Yeon ShinXiao-Jiang Li
Nov 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bernd O EvertUllrich Wüllner
Dec 22, 2006·Journal of Medicinal Chemistry·Stephen A Hitchcock, Lewis D Pennington
Mar 3, 2007·Annual Review of Biochemistry·Myeong Sup Lee, Young-Joon Kim
Apr 19, 2007·Acta Pharmacologica Sinica·Jie CuiZhi-Heng Xu
Sep 21, 2007·Clinical and Experimental Pharmacology & Physiology·Vanessa A MitchellChristopher W Vaughan
Oct 22, 2008·Oncogene·D N Dhanasekaran, E P Reddy
Nov 20, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chun-Wei KuoChing-Fa Yao
Feb 23, 2010·European Journal of Pharmacology·Alp AlptekinMurat Oz
Feb 1, 2011·BMC Biotechnology·Magdalena ZukJan Szopa
Mar 1, 2012·Cellular Signalling·Lucía Cabal-Hierro, Pedro S Lazo
Mar 23, 2012·Immunological Reviews·Sankar Ghosh, Matthew S Hayden
Jun 12, 2012·Acta Neuropathologica·Kay SeidelUdo Rüb
Jul 4, 2012·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Jeannette HübenerHuu Phuc Nguyen
Mar 28, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Kuo-Hsuan ChangChiung-Mei Chen
Jul 16, 2013·Methods in Enzymology·Yong SonHyun-Ock Pae
Apr 5, 2014·Human Molecular Genetics·Han-Yun HsiaoYijuang Chern
Apr 3, 2015·Oxidative Medicine and Cellular Longevity·Roman Fischer, Olaf Maier

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Methods Mentioned

BETA
ELISA
filter trap
NMR
protein assay
electrophoresis
dot-blot

Software Mentioned

ImageXpressMICRO
Metamorph
ChemDraw

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