2. Academic Validation
  3. N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease

N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease

  • Aging Cell. 2024 Feb 21:e14124. doi: 10.1111/acel.14124.
Tao Guo 1,  Lingyan Zhou 1,  Min Xiong 1,  Jing Xiong 1,  Juan Huang 2,  Yiming Li 1,  Guoxin Zhang 1,  Guiqin Chen 1,  Zhi-Hao Wang 1,  Tingting Xiao 1,  Dan Hu 1,  Anyu Bao 3,  Zhentao Zhang 1 4
Affiliations

Affiliations

  • 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
  • 4 TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
PMID: 38380563 DOI: 10.1111/acel.14124
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.

Keywords

Park7; dopaminergic neurons; homocysteine; mitochondrion; oxidative stress.

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