1. N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease.
- Author
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Guo T, Zhou L, Xiong M, Xiong J, Huang J, Li Y, Zhang G, Chen G, Wang ZH, Xiao T, Hu D, Bao A, and Zhang Z
- Subjects
- Humans, Animals, Oxidative Stress drug effects, Mice, Mitochondria metabolism, Protein Deglycase DJ-1 metabolism, Protein Deglycase DJ-1 genetics, Parkinson Disease metabolism, Parkinson Disease pathology, Homocysteine metabolism, Homocysteine analogs & derivatives
- Abstract
DJ-1, also known as Parkinson's disease protein 7 (Park7), is a multifunctional protein that regulates oxidative stress and mitochondrial function. Dysfunction of DJ-1 is implicated in the pathogenesis of Parkinson's disease (PD). Hyperhomocysteinemia is associated with an increased risk of PD. Here we show that homocysteine thiolactone (HTL), a reactive thioester of homocysteine (Hcy), covalently modifies DJ-1 on the lysine 182 (K182) residue in an age-dependent manner. The N-homocysteinylation (N-hcy) of DJ-1 abolishes its neuroprotective effect against oxidative stress and mitochondrial dysfunction, exacerbating cell toxicity. Blocking the N-hcy of DJ-1 restores its protective effect. These results indicate that the N-hcy of DJ-1 abolishes its neuroprotective effect and promotes the progression of PD. Inhibiting the N-hcy of DJ-1 may exert neuroprotective effect against PD., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2024
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