Artículo de revista
Novel Alpha-Synuclein Oligomers Formed with the Aminochrome-Glutathione Conjugate Are Not Neurotoxic
Fecha
2019Registro en:
Neurotoxicity Research, Volumen 35, Issue 2, 2019, Pages 432-440
14763524
10298428
10.1007/s12640-018-9969-0
Autor
Huenchuguala, Sandro
Sjödin, Birgitta
Mannervik, Bengt
Segura-Aguilar, Juan
Institución
Resumen
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.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 determin