The regulatory role of cell cycle exit and neuronal differentiation 1 in the pathogenesis of Parkinson's disease by regulating the nuclear factor kappa B pathway

细胞周期退出和神经元分化1通过调控核因子κB通路在帕金森病发病机制中发挥调控作用

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Abstract

OBJECTIVE: This study seeks to investigate the roles and underlying mechanisms of cell cycle exit and neuronal differentiation 1 (CEND1) on Parkinson's disease. METHODS: Real-time quantitative PCR (RT-qPCR) was employed to assess the expression levels of CEND1 in peripheral blood samples of Parkinson's patients. A cell model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP + )-induced Parkinson's disease was established in-vitro. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assays were used to evaluate the impact of CEND1 on the viability of SH-SY5Y cells induced by MPP + , while flow cytometry was used to assess apoptosis of these cells. The expression of oxidative stress and inflammatory factors in MPP + -treated cells was detected by ELISA. In addition, the effect of CEND1 on Parkinson's disease was interfered by an activator of the nuclear factor kappa B (NF-κB) pathway to clarify the relationship between CEND1 and the NF-κB pathway in a cell model of Parkinson's disease. RESULTS: CEND1 expression is markedly downregulated in patients with Parkinson's disease and cells of the Parkinson's disease model. Downregulation of CEND1-induced apoptosis, inhibited cell proliferation, and promoted expression of inflammatory factors in MPP + -treated cells; however, high expression of CEND1 inhibited MPP + -induced apoptosis, inflammatory factor release, and oxidative stress. In addition, CEND1 inhibited the activation of the NF-κB pathway induced by MPP + , and phorbol 12-myristate 13-acetate reversed the effect of CEND1 on Parkinson's disease. CONCLUSION: CEND1 plays a protective role in the Parkinson's disease cell model by suppressing NF-κB signaling pathway activation, offering a potential target and foundation for the diagnosis and therapy of Parkinson's disease.

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