| First Author | Guo T | Year | 2024 |
| Journal | Aging Cell | Volume | 23 |
| Issue | 5 | Pages | e14124 |
| PubMed ID | 38380563 | Mgi Jnum | J:360560 |
| Mgi Id | MGI:7834536 | Doi | 10.1111/acel.14124 |
| Citation | Guo T, et al. (2024) N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease. Aging Cell 23(5):e14124 |
| abstractText | 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. |
