Pro-survival and anti-inflammatory roles of NF-κB c-Rel in the Parkinson's disease models
Zishan Wang,
Hongtian Dong,
Jinghui Wang,
Yulu Huang,
Xiaoshuang Zhang,
Yilin Tang,
Qing Li,
Zhaolin Liu,
Yuanyuan Ma,
Jiabin Tong,
Li Huang,
Jian Fei,
Mei Yu,
Jian Wang,
Fang Huang
Affiliations
Zishan Wang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Hongtian Dong
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Jinghui Wang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Yulu Huang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Xiaoshuang Zhang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Yilin Tang
Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
Qing Li
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Zhaolin Liu
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Yuanyuan Ma
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Jiabin Tong
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Li Huang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China
Jian Fei
School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China; Shanghai Research Center for Model Organisms, Pudong, Shanghai, 201203, China; Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC., Shanghai, 201203, China
Mei Yu
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China; Corresponding author. State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
Jian Wang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China; Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China; Corresponding author. Department of Neurology, Huashan Hospital, Fudan University. 12 Wulumuqi Zhong Road, Shanghai, 200040, China.
Fang Huang
Department of Translational Neuroscience, Jing’ an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China; Corresponding author. State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
The pathological hallmarks of Parkinson's disease (PD) are the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of overactivated glial cells and neuroinflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) c-Rel subunit is closely related in the pathological progress of PD, however the roles and mechanisms of c-Rel in PD development remain unclear. Here, in neurotoxins-induced PD models, the dynamic changes of NF-κB c-Rel and its functions were evaluated. We found that c-Rel was rapidly activated in the nigrostriatal pathway, which mainly occurred in dopaminergic neurons and microglia. c-Rel could maintain neuronal survival by initiating the anti-apoptotic gene expression in MPP+-treated SH-SY5Y cells and it could inhibit microglial overactivation by suppressing the inflammatory gene expression in LPS-challenged BV2 cells. c-Rel inhibitor IT901 aggravated the damage of MPTP on dopaminergic neurons and promoted the activation of microglia in the nigrostriatal pathway of mice. Moreover, the expression of c-Rel in blood samples of PD patients decreased dramatically. Our results indicate that the NF-κB/c-Rel subunit plays an important role in neuroprotection and neuroinflammation inhibition during PD progression. Keywords: Parkinson's disease, NF-κB/c-Rel, Dopaminergic neurons, Microglia, Neuroprotection, Inflammation
