| First Author | Tripathy D | Year | 2020 |
| Journal | Neurobiol Dis | Volume | 140 |
| Pages | 104849 | PubMed ID | 32222473 |
| Mgi Jnum | J:299295 | Mgi Id | MGI:6449574 |
| Doi | 10.1016/j.nbd.2020.104849 | Citation | Tripathy D, et al. (2020) Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Abeta1-42-mediated toxicity. Neurobiol Dis 140:104849 |
| abstractText | 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-beta 1-42 (Abeta 1-42). The downstream effects of Abeta 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 Abeta-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 Abeta-toxicity, and that its stress-dependent increase makes it suitable for pharmacological intervention. |
