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Novel Alpha-Synuclein Oligomers Formed with the Aminochrome-Glutathione Conjugate Are Not Neurotoxic
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Number of Authors: 42019 (English)In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 35, no 2, p. 432-440Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 35, no 2, p. 432-440
Keywords [en]
Alpha-synuclein, Parkinson's disease, Glutathione, Glutathione transferase, Dopamine, Aminochrome, Oligomers
National Category
Basic Medicine Neurology
Identifiers
URN: urn:nbn:se:su:diva-165639DOI: 10.1007/s12640-018-9969-0ISI: 000455660400014PubMedID: 30343424OAI: oai:DiVA.org:su-165639DiVA, id: diva2:1287039
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved

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