The deglycase activity of DJ-1 mitigates α-synuclein glycation and aggregation in dopaminergic cells: Role of oxidative stress mediated downregulation of DJ-1 in Parkinson's disease

Free Radical Biology & Medicine
Neelam SharmaShasi V Kalivendi

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the degeneration of dopamine neurons of the substantia nigra pars compacta (SNpc) and the presence of intra-neuronal aggregates of α-synuclein and its post-translational products. Based on emerging reports on the association between glycated α-synuclein and PD; and the newly identified deglycase activity of DJ-1, we sought to find the relevance of deglycase activity of DJ-1 on glycation of α-synuclein and its plausible role in PD. Our results demonstrate that DJ-1 has a higher affinity towards the substrate methylglyoxal (MGO) (Km = 900 mM) as compared to its familial mutant, L166P (Km = 1900 mM). Also, CML α-synuclein (CML-syn) served as a substrate for the deglycase activity of DJ-1. Treatment of cells with Parkinsonian mimetic, 1-methyl-4-phenylpyridinium ion (MPP+); oxidants, such as H2O2 and methylglyoxal (MGO) lead to a dose-dependent decrease in the levels of DJ-1 with a concomitant increase in CML-syn. Also, MGO induced cytosolic α-synuclein aggregates in cells which stained positive with the anti-CML antibody. Further, unilateral stereotaxic administration of MGO into the SNpc of mice induced α-synuclein aggregates and CML-syn with a c...Continue Reading

Citations

Aug 5, 2019·Biomolecular NMR Assignments·Letizia Barbieri, Enrico Luchinat
Oct 24, 2019·Protein & Cell·Fang ChengGuang-Hui Liu
Jul 25, 2019·Cells·Cecilia NigroClaudia Miele
Oct 28, 2019·Brain : a Journal of Neurology·Scott P AllenPamela J Shaw
Oct 31, 2019·Future Medicinal Chemistry·Ying ChenChu Wang
Jul 21, 2020·BioMed Research International·Miroslav Pohanka
Nov 17, 2019·International Journal of Molecular Sciences·Kai-Jung LinTsu-Kung Lin
May 21, 2020·Molecular Neurobiology·Aida ZuluetaMarco Trinchera
Feb 10, 2021·Redox Biology·Federica De LazzariMarco Bisaglia
Apr 4, 2021·Cells·Jeswinder Sian-Hulsmann, Peter Riederer
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Sandro PercárioMaria Fani Dolabela
Dec 29, 2020·American Journal of Physiology. Cell Physiology·Ting-Yu ChinSheau-Huei Chueh
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·James N TsoporisThomas G Parker
Jun 27, 2021·Progress in Neurobiology·Maoxin Huang, Shengdi Chen
Jun 27, 2021·Molecular Neurobiology·Charul RajputMahendra Pratap Singh
Jul 7, 2021·Biochemistry. Biokhimii︠a︡·Olga A Buneeva, Alexey E Medvedev
Jun 13, 2021·Progress in Neurobiology·Shuai ZhangXiaofeng Jia
Sep 17, 2021·British Journal of Pharmacology·Md Ezazul HaqueDong-Kug Choi

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