AI Article Synopsis
- * High levels of homocysteine (a type of amino acid) increase the risk of developing PD, and a specific form called homocysteine thiolactone can negatively modify DJ-1 by attaching to a particular site (K182).
- * This modification reduces DJ-1's ability to protect nerve cells from damage, worsening cell toxicity; however, blocking this modification can restore DJ-1's protective effects, suggesting a potential therapeutic target for PD.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113254 | PMC |
| http://dx.doi.org/10.1111/acel.14124 | DOI Listing |
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