Academic Journal

α-Synuclein Negatively Regulates Nurr1 Expression Through NF-κB-Related Mechanism

التفاصيل البيبلوغرافية
العنوان: α-Synuclein Negatively Regulates Nurr1 Expression Through NF-κB-Related Mechanism
المؤلفون: Congcong Jia, Hongqian Qi, Cheng Cheng, Xuefei Wu, Zhaofei Yang, Huaibin Cai, Sheng Chen, Weidong Le
المصدر: Frontiers in Molecular Neuroscience, Vol 13 (2020)
بيانات النشر: Frontiers Media S.A., 2020.
سنة النشر: 2020
المجموعة: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
مصطلحات موضوعية: α-synuclein, nuclear factor κ B (NF-κB), nuclear receptor-related 1 protein (Nurr1), Parkinson’s disease, dopamine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
الوصف: The nuclear receptor-related 1 protein (Nurr1) is critical for the development and survival of midbrain dopamine neurons that are predominantly affected and progressively degenerated in Parkinson’s disease (PD). The expression level of Nurr1 has been proposed to be modulated by α-synuclein (α-SYN), an important pathological hallmark of PD. However, the underlying molecular mechanisms of α-SYN-Nurr1 interaction are still rarely explored. In this study, we investigated the effect and mechanism of α-SYN on the transcription level of Nurr1. Our results showed that overexpression of α-SYN (WT or A53T) reduced Nurr1 and its downstream gene expressions. α-SYN neither affected the mRNA stability nor bound with the promoter of Nurr1, but modulated the transcription activity of Nurr1 promoter region ranging from −605 bp to −418 bp, which contains the binding site of nuclear factor-kappa B (NF-κB). Moreover, overexpression of α-SYN (WT or A53T) down-regulated NF-κB expression level, thereby inhibiting the transcription factor activity of NF-κB and decreasing the binding quantity of NF-κB with Nurr1 promoter. These findings may give us new insights to better understand the molecular mechanisms underlying the α-SYN-regulated Nurr1 function, which may fascinate the investigation of dopamine neuron degeneration in PD pathogenesis.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1662-5099
Relation: https://www.frontiersin.org/article/10.3389/fnmol.2020.00064/full; https://doaj.org/toc/1662-5099
DOI: 10.3389/fnmol.2020.00064
URL الوصول: https://doaj.org/article/d5cf9060c2aa470aa4d12d404a22ee7b
رقم الانضمام: edsdoj.5cf9060c2aa470aa4d12d404a22ee7b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16625099
DOI:10.3389/fnmol.2020.00064