Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Neurochem Int. 2021 Dec;151:105218. doi: 10.1016/j.neuint.2021.105218. Epub 2021 Oct 31.
After ischemic stroke or cardiac arrest, brain ischemia occurs. Currently, no pharmacologic intervention that targets cellular processes has proven effective in improving neurologic outcome in patients after brain ischemia. Recent experimental research has identified the crucial role of proteostasis in survival and recovery of cells after ischemia. In particular, the unfolded protein response (UPR), a key signaling pathway that safeguards cellular proteostasis, is emerging as a promising therapeutic target for brain ischemia. For some time, the UPR has been known to play a critical role in the pathophysiology of brain ischemia; however, only in the recent years has the field grown substantially, largely due to the extensive use of UPR-specific mouse genetic models and the rapidly expanding availability of pharmacologic tools that target the UPR. In this review, we provide a timely update on the progress in our understanding of the UPR in experimental brain ischemia, and discuss the therapeutic implications of targeting the UPR in ischemic stroke and cardiac arrest.
脑缺血发生在缺血性中风或心脏骤停之后。目前，针对细胞过程的药物干预措施并未被证明能有效改善脑缺血患者的神经预后。最近的实验研究已经确定了蛋白质稳态在缺血后细胞存活和恢复中的关键作用。特别是未折叠蛋白反应 (UPR)，一种保护细胞蛋白质稳态的关键信号通路，正在成为脑缺血的一个有前途的治疗靶点。一段时间以来，人们已经知道 UPR 在脑缺血的病理生理学中起着关键作用；然而，直到近年来，该领域才取得了实质性的发展，这主要归因于 UPR 特异性小鼠遗传模型的广泛应用以及针对 UPR 的药理学工具的迅速普及。在这篇综述中，我们及时更新了对实验性脑缺血中 UPR 的理解进展，并讨论了针对 UPR 在缺血性中风和心脏骤停中的治疗意义。
