Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea.
BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Cells. 2020 Sep 2;9(9):2020. doi: 10.3390/cells9092020.
The 70 kDa heat shock protein (HSP70) is a stress-inducible protein that has been shown to protect the brain from various nervous system injuries. It allows cells to withstand potentially lethal insults through its chaperone functions. Its chaperone properties can assist in protein folding and prevent protein aggregation following several of these insults. Although its neuroprotective properties have been largely attributed to its chaperone functions, HSP70 may interact directly with proteins involved in cell death and inflammatory pathways following injury. Through the use of mutant animal models, gene transfer, or heat stress, a number of studies have now reported positive outcomes of HSP70 induction. However, these approaches are not practical for clinical translation. Thus, pharmaceutical compounds that can induce HSP70, mostly by inhibiting HSP90, have been investigated as potential therapies to mitigate neurological disease and lead to neuroprotection. This review summarizes the neuroprotective mechanisms of HSP70 and discusses potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease.
70 kDa 热休克蛋白（HSP70）是一种应激诱导蛋白，已被证明可保护大脑免受各种神经系统损伤。它通过伴侣功能使细胞能够承受潜在的致命损伤。在受到几种损伤后，其伴侣特性可以协助蛋白质折叠并防止蛋白质聚集。尽管其神经保护特性主要归因于其伴侣功能，但 HSP70 可能会在损伤后直接与参与细胞死亡和炎症途径的蛋白质相互作用。通过使用突变动物模型、基因转移或热应激，许多研究现在已经报告了 HSP70 诱导的积极结果。然而，这些方法在临床转化方面并不实用。因此，已研究了能够诱导 HSP70 的药物化合物，主要通过抑制 HSP90，作为减轻神经疾病和导致神经保护的潜在治疗方法。本综述总结了 HSP70 的神经保护机制，并讨论了通过药理学手段实际诱导这种内源性治疗分子的潜在方法，最终改善急性神经疾病中的神经学结果。
