YTHDC1 通过破坏 PTEN mRNA 促进 Akt 磷酸化从而减轻脑缺血性中风。
YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA.
机构信息
Department of Interventional Radiology, the Affiliated Hospital of Qingdao University, Jiangsu Road 16, Qingdao, 266000, Shandong, China.
出版信息
Cell Death Dis. 2020 Nov 13;11(11):977. doi: 10.1038/s41419-020-03186-2.
YTH Domain Containing 1 (YTHDC1) is one of the mA readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating mA reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.
YTH 结构域包含蛋白 1（YTHDC1）是一种必需的 mA 读取器，对于卵母细胞发育和肿瘤进展至关重要。YTHDC1 在神经元存活和缺血性中风中的作用尚不清楚。在这里，我们发现 YTHDC1 在缺血性中风的早期阶段不受调节。YTHDC1 的敲低加重了缺血性脑损伤，而过表达 YTHDC1 则保护大鼠免受脑损伤。在机制上，YTHDC1 促进 PTEN mRNA 的降解，增加 Akt 磷酸化，从而促进神经元存活，尤其是在缺血后。这些数据将 YTHDC1 确定为神经元存活的新调节剂，调节 mA 读取器 YTHDC1 可能为缺血性中风提供一个潜在的治疗靶点。
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