当前位置：
X-MOL 学术
›
Neurobiol. Dis.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1-42-mediated toxicity.
Neurobiology of Disease ( IF 5.1 ) Pub Date : 2020-03-25 , DOI: 10.1016/j.nbd.2020.104849 Debasmita Tripathy 1 , Alice Migazzi 1 , Federica Costa 1 , Alessandro Roncador 1 , Pamela Gatto 1 , Federica Fusco 2 , Lucia Boeri 3 , Diego Albani 2 , J Leon Juárez-Hernández 4 , Carlo Musio 4 , Laura Colombo 5 , Mario Salmona 5 , M M Micha Wilhelmus 6 , Benjamin Drukarch 6 , Maria Pennuto 7 , Manuela Basso 1
Neurobiology of Disease ( IF 5.1 ) Pub Date : 2020-03-25 , DOI: 10.1016/j.nbd.2020.104849 Debasmita Tripathy 1 , Alice Migazzi 1 , Federica Costa 1 , Alessandro Roncador 1 , Pamela Gatto 1 , Federica Fusco 2 , Lucia Boeri 3 , Diego Albani 2 , J Leon Juárez-Hernández 4 , Carlo Musio 4 , Laura Colombo 5 , Mario Salmona 5 , M M Micha Wilhelmus 6 , Benjamin Drukarch 6 , Maria Pennuto 7 , Manuela Basso 1
Affiliation
|
Alzheimer's disease (AD) is the most common cause of dementia. At the pre-symptomatic phase of the disease, the processing of the amyloid precursor protein (APP) produces toxic peptides, called amyloid-β 1-42 (Aβ 1-42). The downstream effects of Aβ 1-42 production are not completely uncovered. Here, we report the involvement of transglutaminase 1 (TG1) in in vitro AD models of neuronal toxicity. TG1 was increased at late stages of the disease in the hippocampus of a mouse model of AD and in primary cortical neurons undergoing stress. Silencing of TGM1 gene was sufficient to prevent Aβ-mediated neuronal death. Conversely, its overexpression enhanced cell death. TGM1 upregulation was mediated at the transcriptional level by an activator protein 1 (AP1) binding site that when mutated halted TGM1 promoter activation. These results indicate that TG1 acts downstream of Aβ-toxicity, and that its stress-dependent increase makes it suitable for pharmacological intervention.
中文翻译：
在神经元应激和Aβ1-42介导的毒性的体外模型中，转谷氨酰胺酶1转录的增加介导了神经元死亡。
阿尔茨海默氏病（AD）是痴呆症的最常见原因。在疾病的症状前期，淀粉样蛋白前体蛋白（APP）的加工会产生有毒肽，称为淀粉样蛋白β1-42（Aβ1-42）。尚未完全发现Aβ1-42产生的下游影响。在这里，我们报告转谷氨酰胺酶1（TG1）参与神经毒性的体外AD模型。TG1在疾病的晚期在AD小鼠模型的海马中和处于应激状态的原代皮层神经元中增加。TGM1基因的沉默足以预防Aβ介导的神经元死亡。相反，其过表达增加了细胞死亡。TGM1上调在转录水平由激活蛋白1（AP1）结合位点介导，该位点发生突变时会终止TGM1启动子的激活。
更新日期：2020-03-26
中文翻译：
在神经元应激和Aβ1-42介导的毒性的体外模型中，转谷氨酰胺酶1转录的增加介导了神经元死亡。
阿尔茨海默氏病（AD）是痴呆症的最常见原因。在疾病的症状前期，淀粉样蛋白前体蛋白（APP）的加工会产生有毒肽，称为淀粉样蛋白β1-42（Aβ1-42）。尚未完全发现Aβ1-42产生的下游影响。在这里，我们报告转谷氨酰胺酶1（TG1）参与神经毒性的体外AD模型。TG1在疾病的晚期在AD小鼠模型的海马中和处于应激状态的原代皮层神经元中增加。TGM1基因的沉默足以预防Aβ介导的神经元死亡。相反，其过表达增加了细胞死亡。TGM1上调在转录水平由激活蛋白1（AP1）结合位点介导，该位点发生突变时会终止TGM1启动子的激活。
京公网安备 11010802027423号