A novel compound alleviates oxidative stress via PKA/CREB1-mediated DJ-1 upregulation

被引：0

作者：

Pan, Hong ^{[1
,2
,3
]}

Huang, Maoxin ^{[1
,2
]}

Zhu, Chenxiang ^{[3
]}

Lin, Suzhen ^{[1
,2
]}

He, Lu ^{[1
,2
]}

Shen, Ruinan ^{[1
,2
]}

Chen, Yimeng ^{[1
,2
]}

Fang, Fang ^{[1
,2
]}

Qiu, Yinghui ^{[1
,2
]}

Qin, Meiling ^{[4
,5
]}

Bao, Puhua ^{[4
,5
]}

Tan, Yuyan ^{[1
,2
]}

Xu, Jin ^{[4
,5
]}

Ding, Jianqing ^{[1
,2
]}

Chen, Shengdi ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Neurol, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Inst Neurol, Sch Med, Shanghai 200025, Peoples R China

[3] Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Lab Translat Res Neurodegenerat Dis, Shanghai, Peoples R China

[4] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China

[5] Chinese Acad Sci, State key Lab Neurosci, Shanghai 200031, Peoples R China

来源：

JOURNAL OF NEUROCHEMISTRY | 2024年 / 168卷 / 09期

基金：

中国国家自然科学基金;

关键词：

CREB1; DJ-1; oxidative stress; Parkinson's disease; small compounds; PARKINSONS-DISEASE; BINDING; CREB; PATHWAY; PROTEIN; EXPRESSION; APOPTOSIS; DOPAMINE; MODEL; INVOLVEMENT;

D O I：

10.1111/jnc.16161

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.image

引用

页码：3034 / 3049

页数：16