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NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1.
| Content Provider | Europe PMC |
|---|---|
| Author | Zhu, Jie Yang, Li-Kun Wang, Qiu-Hong Lin, Wei Feng, Yi Xu, Ye-Ping Chen, Wei-Liang Xiong, Kun Wang, Yu-Hai |
| Copyright Year | 2020 |
| Abstract | Cerebral ischemia results in severe brain damage, and is a leading cause of death and long-term disability. Previous studies have investigated methods to activate astrocytes in order to promote repair in injured brain tissue and inhibit cell death. It has previously been shown that N-myc downstream-regulated gene 2 (NDRG2) was highly expressed in astrocytes and associated with cell activity, but the underlying mechanism is largely unknown. The present study generated NDRG2 conditional knockout (Ndrg2-/-) mice to investigate whether NDRG2 can block ischemia-induced astrocyte necroptosis by suppressing receptor interacting protein kinase 1 (RIPK1) expression. This study investigated astrocyte activity in cerebral ischemia, and identified that ischemic brain injuries could trigger RIP-dependent astrocyte necroptosis. The depletion of NDRG2 was found to accelerate permanent middle cerebral artery occlusion-induced necroptosis in the brain tissue of Ndrg2-/- mice, indicating that NDRG2 may act as a neuroprotector during cerebral ischemic injury. The present study suggested that NDRG2 attenuated astrocytic cell death via the suppression of RIPK1. The pharmacological inhibition of astrocyte necroptosis by necrostatin-1 provided neuroprotection against ischemic brain injuries after NDRG2 knockdown. Therefore, NDRG2 could be considered as a potential target for the treatment of cerebral ischemia. |
| ISSN | 17912997 |
| Journal | Molecular Medicine Reports |
| Volume Number | 22 |
| PubMed Central reference number | PMC7453600 |
| Issue Number | 4 |
| PubMed reference number | 32945444 |
| e-ISSN | 17913004 |
| DOI | 10.3892/mmr.2020.11421 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2020-08-07 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Zhu et al. |
| Subject Keyword | N-myc downstream-regulated gene 2 receptor interacting protein kinase 1 necroptosis necrostatin-1 astrocyte |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Molecular Biology Biochemistry Cancer Research Molecular Medicine Oncology |
