N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease
© 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Aging cell - (2024) vom: 21. Feb., Seite e14124 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Tao [VerfasserIn] |
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| Links: |
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| Themen: |
Dopaminergic neurons |
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| Anmerkungen: |
Date Revised 21.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/acel.14124 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368705870 |
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| 520 | |a © 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a dopaminergic neurons | |
| 650 | 4 | |a homocysteine | |
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| 700 | 1 | |a Zhou, Lingyan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yiming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Guoxin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Guiqin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhi-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Anyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhentao |e verfasserin |4 aut | |
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