Disulfide cross-linked protein represents a significant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice.

Proceedings of the National Academy of Sciences of the United States of America
Yoshiaki FurukawaThomas V O'Halloran

Abstract

Point mutations in Cu, Zn-superoxide dismutase (SOD1) cause a familial form of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Aggregates of mutant SOD1 proteins are observed in histopathology and are invoked in several proposed mechanisms for motor neuronal death; however, the significant stability and activity of the mature mutant proteins are not readily explained in such models. Recent biochemical studies suggest that it is the immature disulfide-reduced forms of the familial ALS mutant SOD1 proteins that play a critical role; these forms tend to misfold, oligomerize, and readily undergo incorrect disulfide formation upon mild oxidative stress in vitro. Here we provide physiological support for this mechanism of aggregate formation and show that a significant fraction of the insoluble SOD1 aggregates in spinal cord of the ALS-model transgenic mice contain multimers cross-linked via intermolecular disulfide bonds. These insoluble disulfide-linked SOD1 multimers are found only in the spinal cord of symptomatic transgenic animals, are not observed in unafflicted tissue such as brain cortex and liver, and can incorporate WT SOD1 protein. The findings provide a biochemical basis for a pathological hallmark of ...Continue Reading

References

Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·M E RippsJ W Gordon
Aug 16, 1994·Proceedings of the National Academy of Sciences of the United States of America·D R BorcheltD W Cleveland
May 6, 1994·Journal of Molecular Biology·D BordoM Bolognesi
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J A JohnstonR R Kopito
Nov 21, 2001·Nature Reviews. Neuroscience·D W Cleveland, J D Rothstein
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ayako Okado-Matsumoto, Irwin Fridovich
Dec 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mikael J LindbergMikael Oliveberg
May 16, 2003·The Journal of Biological Chemistry·Lori Sturtz FieldValeria Cizewski Culotta
May 20, 2003·Nature Structural Biology·Jennifer Stine ElamP John Hart
May 22, 2003·Free Radical Biology & Medicine·Stefan I Liochev, Irwin Fridovich
Oct 10, 2003·Brain : a Journal of Neurology·P Andreas JonssonStefan L Marklund
Apr 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Michael A HoughS Samar Hasnain
Apr 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nina M BrownThomas V O'Halloran
Jun 3, 2004·The Journal of Comparative Neurology·Patrick G SullivanStephen W Scheff
Jun 25, 2004·The EMBO Journal·Yoshiaki FurukawaThomas V O'Halloran
Oct 8, 2004·The EMBO Journal·Carina I HolmbergRichard I Morimoto
Oct 12, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sagar D KhareNikolay V Dokholyan
Nov 4, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mikael J LindbergMikael Oliveberg
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Soumya S RayPeter T Lansbury
Dec 7, 2005·Brain : a Journal of Neurology·P Andreas JonssonStefan L Marklund
Apr 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Han-Xiang DengTeepu Siddique

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Citations

Nov 15, 2011·Journal of Bioenergetics and Biomembranes·Maria Teresa Carrì, Mauro Cozzolino
Jun 21, 2008·Neuromolecular Medicine·P Hemachandra Reddy
Dec 19, 2012·Journal of the American Society for Mass Spectrometry·Timothy W RhoadsJoseph S Beckman
Jul 24, 2008·Chemical Society Reviews·A I Anzellotti, N P Farrell
Nov 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Madhuri ChattopadhyayJoan Selverstone Valentine
Apr 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia BanciMiguela Vieru
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Celeste M KarchDavid R Borchelt
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jared R AuclairJeffrey N Agar
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Leslie I GradNeil R Cashman
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Rachel TeslaAndrew A Pieper
Jul 29, 2010·The Journal of Biological Chemistry·Mary Anne SahawnehAlvaro G Estévez
Aug 2, 2006·The Journal of Biological Chemistry·Mark C CarrollValeria Cizewski Culotta
Mar 29, 2008·Antioxidants & Redox Signaling·Mauro CozzolinoMaria Teresa Carrì
Jul 29, 2009·Antioxidants & Redox Signaling·Merridee A WoutersNaomi L Haworth
Apr 7, 2009·Antioxidants & Redox Signaling·Mauro CozzolinoMaria Teresa Carrì
Jun 22, 2010·Antioxidants & Redox Signaling·Melissa NassifClaudio Hetz
Feb 24, 2009·Human Molecular Genetics·Lijun WangRaymond P Roos
Sep 11, 2010·Human Molecular Genetics·Alberto FerriMaria Teresa Carrì
Jul 26, 2012·Neurology Research International·Yoshiaki Furukawa
Feb 23, 2010·BMC Neuroscience·David A ElliottBrett Garner
Jun 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lucia BanciJulian P Whitelegge
Jul 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Arie GruzmanJian Liu
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Per ZetterströmStefan L Marklund
Aug 29, 2013·International Journal of Cell Biology·Maria Francesca Mossuto
Oct 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ashley J PrattElizabeth D Getzoff
Mar 28, 2013·Oxidative Medicine and Cellular Longevity·Sonam ParakhJulie D Atkin

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