Iron-induced oxidative stress contributes to α-synuclein phosphorylation and up-regulation via polo-like kinase 2 and casein kinase 2

Neurochemistry International
Ranran WangJunxia Xie

Abstract

α-Synuclein plays a central role in synucleinopathies pathogenesis such as Parkinson's disease (PD). Phosphorylation is the most common and important protein modification linked to α-synuclein pathologies. There is mounting evidence suggested iron and α-synuclein are closely related in PD. We previously reported iron up-regulated α-synuclein mRNA levels and induced α-synuclein aggregation. In the present study, we aimed to investigate whether and how phosphorylation was involved in iron-induced α-synuclein regulations. The results showed that iron could induce pS129 α-synuclein (phosphorylation at Ser129) and α-synuclein upregulation in the substantia nigra of iron-overloaded rats and iron-treated SH-SY5Y cells, accompanied by the elevated levels of polo-like kinase 2 (PLK2) and casein kinase 2 (CK2). Over-expression of CK2 or PLK2 induced pS129 α-synuclein up-regulation and inhibitors of CK2 or PLK2 could suppress iron-induced α-synuclein phosphorylation. Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 α-synuclein levels, indicating oxidative stress plays a critical role in iron-induced α-synuclein phosphorylation. However, iron-induced α-synuclein up-regulation could only be partially blocke...Continue Reading

Citations

Mar 7, 2020·Biomolecules·Margaux TeilBenjamin Dehay
Sep 4, 2020·Experimental Biology and Medicine·Santosh R D'Mello, Mark C Kindy
Mar 27, 2020·International Journal of Molecular Sciences·Yasushi YabukiKohji Fukunaga
Jul 8, 2020·Antioxidants·Han-A Park, Amy C Ellis
Mar 26, 2021·European Journal of Medicinal Chemistry·Zheng ZhangTingting Liu
Apr 13, 2021·Critical Reviews in Biochemistry and Molecular Biology·Christian BorgoMauro Salvi
Jan 7, 2020·Molecular Therapy. Nucleic Acids·Duo ZhaoXiufen Zheng
Dec 7, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hui XiongYoucai Zhang

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