Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine.

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  • Additional Information
    • Publication Year:
      2013
    • Author-Supplied Keywords:
      Research Article
    • NAICS/Industry Codes:
      NAICS/Industry Codes 416210 Metal service centres
      331110 Iron and Steel Mills and Ferroalloy Manufacturing
      112990 All Other Animal Production
    • Abstract:
      Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the huntingtin gene. Iron accumulates in the brains of HD patients and mouse disease models. However, the cellular and subcellular sites of iron accumulation, as well as significance to disease progression are not well understood. We used independent approaches to investigate the location of brain iron accumulation. In R6/2 HD mouse brain, synchotron x-ray fluorescence analysis revealed iron accumulation as discrete puncta in the perinuclear cytoplasm of striatal neurons. Further, perfusion Turnbull’s staining for ferrous iron (II) combined with transmission electron microscope ultra-structural analysis revealed increased staining in membrane bound peri-nuclear vesicles in R6/2 HD striatal neurons. Analysis of iron homeostatic proteins in R6/2 HD mice revealed decreased levels of the iron response proteins (IRPs 1 and 2) and accordingly decreased expression of iron uptake transferrin receptor (TfR) and increased levels of neuronal iron export protein ferroportin (FPN). Finally, we show that intra-ventricular delivery of the iron chelator deferoxamine results in an improvement of the motor phenotype in R6/2 HD mice. Our data supports accumulation of redox-active ferrous iron in the endocytic / lysosomal compartment in mouse HD neurons. Expression changes of IRPs, TfR and FPN are consistent with a compensatory response to an increased intra-neuronal labile iron pool leading to increased susceptibility to iron-associated oxidative stress. These findings, together with protection by deferoxamine, support a potentiating role of neuronal iron accumulation in HD. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • ISSN:
      19326203
    • Accession Number:
      94478894
  • Citations
    • ABNT:
      CHEN, J. et al. Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine. PLoS ONE, [s. l.], v. 8, n. 10, p. 1, 2013. Disponível em: . Acesso em: 25 ago. 2019.
    • AMA:
      Chen J, Marks E, Lai B, et al. Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine. PLoS ONE. 2013;8(10):1. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894. Accessed August 25, 2019.
    • APA:
      Chen, J., Marks, E., Lai, B., Zhang, Z., Duce, J. A., Lam, L. Q., … Fox, J. H. (2013). Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine. PLoS ONE, 8(10), 1. Retrieved from http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894
    • Chicago/Turabian: Author-Date:
      Chen, Jianfang, Eileen Marks, Barry Lai, Zhaojie Zhang, James A. Duce, Linh Q. Lam, Irene Volitakis, Ashley I. Bush, Steven Hersch, and Jonathan H. Fox. 2013. “Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine.” PLoS ONE 8 (10): 1. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894.
    • Harvard:
      Chen, J. et al. (2013) ‘Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine’, PLoS ONE, 8(10), p. 1. Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894 (Accessed: 25 August 2019).
    • Harvard: Australian:
      Chen, J, Marks, E, Lai, B, Zhang, Z, Duce, JA, Lam, LQ, Volitakis, I, Bush, AI, Hersch, S & Fox, JH 2013, ‘Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine’, PLoS ONE, vol. 8, no. 10, p. 1, viewed 25 August 2019, .
    • MLA:
      Chen, Jianfang, et al. “Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine.” PLoS ONE, vol. 8, no. 10, Oct. 2013, p. 1. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894.
    • Chicago/Turabian: Humanities:
      Chen, Jianfang, Eileen Marks, Barry Lai, Zhaojie Zhang, James A. Duce, Linh Q. Lam, Irene Volitakis, Ashley I. Bush, Steven Hersch, and Jonathan H. Fox. “Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine.” PLoS ONE 8, no. 10 (October 2013): 1. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894.
    • Vancouver/ICMJE:
      Chen J, Marks E, Lai B, Zhang Z, Duce JA, Lam LQ, et al. Iron Accumulates in Huntington’s Disease Neurons: Protection by Deferoxamine. PLoS ONE [Internet]. 2013 Oct [cited 2019 Aug 25];8(10):1. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=94478894