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01-02-2019 | ORIGINAL ARTICLE

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

Authors: Sandro Huenchuguala, Birgitta Sjödin, Bengt Mannervik, Juan Segura-Aguilar

Published in: Neurotoxicity Research | Issue 2/2019

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.

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Title: Novel Alpha-Synuclein Oligomers Formed with the Aminochrome-Glutathione Conjugate Are Not Neurotoxic
Authors: Sandro Huenchuguala
Birgitta Sjödin
Bengt Mannervik
Juan Segura-Aguilar
Publication date: 01-02-2019
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 2/2019
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-018-9969-0

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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