Academic Journal
Restoration of ER proteostasis attenuates remote apoptotic cell death after spinal cord injury by reducing autophagosome overload
| العنوان: | Restoration of ER proteostasis attenuates remote apoptotic cell death after spinal cord injury by reducing autophagosome overload |
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| المؤلفون: | Bisicchia, Elisa, Mastrantonio, Roberta, Nobili, Annalisa, Palazzo, Claudia, La Barbera, Livia, Latini, Laura, Millozzi, Francesco, Sasso, Valeria, Palacios, Daniela, D’Amelio, Marcello, Viscomi, Maria Teresa |
| المصدر: | Cell Death & Disease ; volume 13, issue 4 ; ISSN 2041-4889 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | The pathogenic mechanisms that underlie the progression of remote degeneration after spinal cord injury (SCI) are not fully understood. In this study, we examined the relationship between endoplasmic reticulum (ER) stress and macroautophagy, hereafter autophagy, and its contribution to the secondary damage and outcomes that are associated with remote degeneration after SCI. Using a rat model of spinal cord hemisection at the cervical level, we measured ER stress and autophagy markers in the axotomized neurons of the red nucleus (RN). In SCI animals, mRNA and protein levels of markers of ER stress, such as GRP78, CHOP, and GADD34, increased 1 day after the injury, peaking on Day 5. Notably, in SCI animals, the increase of ER stress markers correlated with a blockade in autophagic flux, as evidenced by the increase in microtubule-associated protein 2 light chain 3 (LC3-II) and p62/SQSTM1 (p62) and the decline in LAMP1 and LAMP2 levels. After injury, treatment with guanabenz protected neurons from UPR failure and increased lysosomes biogenesis, unblocking autophagic flux. These effects correlated with greater activation of TFEB and improved neuronal survival and functional recovery—effects that persisted after suspension of the treatment. Collectively, our results demonstrate that in remote secondary damage, impairments in autophagic flux are intertwined with ER stress, an association that contributes to the apoptotic cell death and functional damage that are observed after SCI. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41419-022-04830-9 |
| الاتاحة: | http://dx.doi.org/10.1038/s41419-022-04830-9 https://www.nature.com/articles/s41419-022-04830-9.pdf https://www.nature.com/articles/s41419-022-04830-9 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.C654CE7F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41419-022-04830-9 |
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