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EnglishAlzheimer'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.
Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1–42-mediated toxicity / Tripathy, D.; Migazzi, A.; Costa, F.; Roncador, A.; Gatto, P.; Fusco, F.; Boeri, L.; Albani, D.; Juarez-Hernandez, J. L.; Musio, C.; Colombo, L.; Salmona, M.; Wilhelmus, M. M. M.; Drukarch, B.; Pennuto, M.; Basso, M.. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 140:(2020), pp. 10484901-10484910. [10.1016/j.nbd.2020.104849]
| Titolo: | Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1–42-mediated toxicity | |
| Autori: | Tripathy, D.; Migazzi, A.; Costa, F.; Roncador, A.; Gatto, P.; Fusco, F.; Boeri, L.; Albani, D.; Juarez-Hernandez, J. L.; Musio, C.; Colombo, L.; Salmona, M.; Wilhelmus, M. M. M.; Drukarch, B.; Pennuto, M.; Basso, M. | |
| Autori Unitn: | ||
| Titolo del periodico: | NEUROBIOLOGY OF DISEASE | |
| Anno di pubblicazione: | 2020 | |
| Codice identificativo Scopus: | 2-s2.0-85082745781 | |
| Codice identificativo Pubmed: | 32222473 | |
| Codice identificativo WOS: | WOS:000538117900009 | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.nbd.2020.104849 | |
| Handle: | http://hdl.handle.net/11572/334867 | |
| Citazione: | Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1–42-mediated toxicity / Tripathy, D.; Migazzi, A.; Costa, F.; Roncador, A.; Gatto, P.; Fusco, F.; Boeri, L.; Albani, D.; Juarez-Hernandez, J. L.; Musio, C.; Colombo, L.; Salmona, M.; Wilhelmus, M. M. M.; Drukarch, B.; Pennuto, M.; Basso, M.. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 140:(2020), pp. 10484901-10484910. [10.1016/j.nbd.2020.104849] | |
| Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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