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Neurotoxicity Research

, Volume 35, Issue 2, pp 432–440 | Cite as

Novel Alpha-Synuclein Oligomers Formed with the Aminochrome-Glutathione Conjugate Are Not Neurotoxic

  • Sandro Huenchuguala
  • Birgitta Sjödin
  • Bengt Mannervik
  • Juan Segura-AguilarEmail author
ORIGINAL ARTICLE

Abstract

Aminochrome induces neurotoxic alpha-synuclein oligomer formation relevant to the etiology of Parkinson’s disease. Oxidative stress produces aminochrome from dopamine, but conjugation with glutathione catalyzed by glutathione transferase M2-2 significantly decreases aminochrome-induced toxicity and alpha-synuclein oligomer formation. Notably, in the presence of the aminochrome-glutathione conjugate, previously unknown species of alpha-synuclein oligomers are formed. These aminochrome-glutathione oligomers of alpha-synuclein differ from formerly characterized oligomers and (i) have high molecular weight, and are stable and SDS-resistant, as determined by the Western blot method, (ii) show positive NBT-quinone-protein staining, which indicates the formation of alpha-synuclein adducts containing aminochrome. Furthermore, aminochrome-glutathione alpha-synuclein oligomers (iii) have distinctive shape and size, as determined by transmission electron microscopy, and (iv) are not toxic in U373MG cells. In conclusion, glutathione conjugated with aminochrome induces a new type of alpha-synuclein oligomers of a different size and shape, which have no demonstrable toxicity.

Keywords

Alpha-synuclein Parkinson’s disease Glutathione Glutathione transferase Dopamine Aminochrome Oligomers 

Notes

Funding information

This study was supported through funding from FONDECYT (1100165, 1061083, 1120337, 7040028, 1170033), and a CONICYT doctoral scholarship and a doctoral thesis support scholarship no. 24121454, as well as by the Swedish Research Council.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sandro Huenchuguala
    • 1
    • 2
  • Birgitta Sjödin
    • 3
  • Bengt Mannervik
    • 3
  • Juan Segura-Aguilar
    • 1
    Email author
  1. 1.Molecular and Clinical Pharmacology, ICBM, Faculty of MedicineUniversity of ChileSantiago-7Chile
  2. 2.Escuela de Tecnología Médica, Facultad de SaludUniversidad Santo TomásOsornoChile
  3. 3.Department of Biochemistry and BiophysicsStockholm UniversityStockholmSweden

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