| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 140, Iss , Pp 104849- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2020.104849 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full Text from ScienceDirect