PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction.
PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction.
Where did the research take place?
Possible study sites were matched from the text; these need review.
Time, NO · Possible study site
To clarify the temporal relationship between PRMT9 upregulation and DUSP26 downregulation, we performed a time‑course analysis in SH‑SY5Y cells exposed to MPP+.Location evidence
Green, US · Possible study site
(A) Double immunofluorescence of PRMT9 (green) and TH (DA neuron marker, red) were performed in SN of mouse brain after MPTP treatment.Location evidence
Shanghai, CN · Possible study site
HEK 293T cells and SH‐SY5Y cells were purchased from the Cell Center of Chinese Academy of Sciences (Shanghai, China) and maintained in DMEM (Meilunbio, Cat.Location evidence
Jinan, CN · Author affiliation
Department of Pharmacology, School of Basic Medical Sciences and Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.Location evidence
Beijing, CN · Author affiliation
Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, P. R. China.Location evidence
Shenzhen, CN · Author affiliation
Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong, P. R. China.Location evidence
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Original abstract
Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and play a crucial role in the pathogenesis of diseases. Mitochondrial dysfunction is implicated in the neurodegeneration of Parkinson's disease (PD). However, whether protein arginine methyltransferase 9 (PRMT9), which is found in mitochondria, is involved in PD remains unclear. In this study, we found that PRMT9 was markedly increased in the nigrostriatal region of PD mice induced by MPTP and in SH-SY5Y cells stimulated with MPP+. In MPP+-exposed SH-SY5Y cells, PRMT9 translocated to mitochondria and exacerbated mitochondrial injury, manifested as decreased mitochondrial membrane potential, reduced ATP production, elevated ROS levels, and mitochondrial fragmentation. Furthermore, PRMT9 deficiency significantly alleviated dopaminergic (DA) neurodegeneration induced by MPTP, while PRMT9 overexpression aggravated MPTP-induced neurodegeneration. Mechanistically, PRMT9 directly interacted with dual-specificity phosphatase 26 (DUSP26) and catalyzed its arginine methylation at residue R29, which then promoted the polyubiquitination and proteasomal degradation of DUSP26 mediated by Trim32. Therefore, PRMT9 drove DA neurodegeneration in PD by promoting DUSP26 degradation and inducing mitochondrial dysfunction. Our study identified PRMT9 as a novel potential therapeutic target and a pharmaceutical intervention targeting the interaction between PRMT9 and DUSP26 may provide a promising strategy for PD.