TY - JOUR AB - 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. AD - Department of Neurosurgery, The 101 Hospital of PLA, School of Medicine, Anhui Medical University, Wuxi, Jiangsu 214044, P.R. China Department of Ophthalmology, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, P.R. China AU - Zhu,Jie AU - Yang,Li-Kun AU - Wang,Qiu-Hong AU - Lin,Wei AU - Feng,Yi AU - Xu,Ye-Ping AU - Chen,Wei-Liang AU - Xiong,Kun AU - Wang,Yu-Hai DA - 2020/10/01 DO - 10.3892/mmr.2020.11421 EP - 3110 IS - 4 JO - Mol Med Rep KW - N-myc downstream-regulated gene 2 receptor interacting protein kinase 1 necroptosis necrostatin-1 astrocyte PY - 2020 SN - 1791-2997 1791-3004 SP - 3103 ST - NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1 T2 - Molecular Medicine Reports TI - NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1 UR - https://doi.org/10.3892/mmr.2020.11421 VL - 22 ER -