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Merck
CN
  • Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1-42-mediated toxicity.

Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1-42-mediated toxicity.

Neurobiology of disease (2020-03-31)
Debasmita Tripathy, Alice Migazzi, Federica Costa, Alessandro Roncador, Pamela Gatto, Federica Fusco, Lucia Boeri, Diego Albani, J Leon Juárez-Hernández, Carlo Musio, Laura Colombo, Mario Salmona, M M Micha Wilhelmus, Benjamin Drukarch, Maria Pennuto, Manuela Basso
摘要

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.

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Sigma-Aldrich
L-谷氨酸 单钠盐 水合物, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
单克隆抗 β-微管蛋白 I 小鼠抗, clone SAP.4G5, ascites fluid