Degradation of BRD4 protein with dBET1 inhibits neurotoxic effects of α-synuclein oligomers
10.3969/j.issn.1009-0126.2024.05.021
- VernacularTitle:dBET1降解溴结构域蛋白4抑制α突触核蛋白寡聚体的神经毒性作用研究
- Author:
Yinjuan ZHENG
1
;
Piao ZHANG
;
Peiting HUANG
;
Yuhu ZHANG
Author Information
1. 510006 广州,华南理工大学医学院
- Keywords:
Parkinson disease;
bromodomain containing proteins;
synucleins;
NF-E2-related factor 2;
oxidative stress;
neuritis;
dBET 1
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(5):573-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether degradation of bromodomain-containing protein 4(BRD4)protein with dBET1 can inhibit neuroinflammation and oxidative stress caused byα-synuclein(α-syn)oligomers.Methods After BV2 cells or SH-SY5Y cells were treated with dBET1 and α-syn oligomers,the cells were divided into Control group,α-syn group,α-syn+500 and 1000 nmol/L dBET1 groups,and dBET1 group(1000 nmol/L).Real-time quantitative fluo-rescent PCR(qPCR)was used to detect the expression of inflammatory factors and anti-inflam-matory factors,and Western blotting was employed to measure the expression of BRD4,nuclear factor 2 associated factor 2(Nrf2),phosphorylated nuclear transcription factor-κB(p-NF-κB)and phosphorylated α-synuclein(p-α-synuclein).Results The α-syn+1000 nmol/L dBET1 group had lower mRNA levels of inflammatory factors and reduced protein levels of BRD4,p-NF-κB and p-α-synuclein,but higher mRNA levels of anti-inflammatory factors and decreased Nrf2 protein level(2.02±0.14 vs 0.96±0.24,P＜0.05)when compared with the α-syn group.Conclusion dBET1 can inhibit neuroinflammation and oxidative stress caused by α-synuclein through p-NF-KB and Nrf2 to a certain extent,which further provides a theoretical basis for its application in the treatment of Parkinson's disease.
