Department of Neurology, University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, 127 Neurology, VAMC, 4150 Clement St., San Francisco, CA 94121, USA.
Inflammopharmacology. 2012 Jun;20(3):177-85. doi: 10.1007/s10787-011-0115-3. Epub 2012 Jan 13.
The 70-kDa heat shock protein (Hsp70) is thought to protect the brain from a variety of insults. Although the mechanism has been largely limited to its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory pathways. Brain injury and ischemia are associated with an immune response that is largely innate. Hsp70 appears to suppress this response and lead to improved neurological outcome. However, most of this work has relied on the use of genetic mutant models or Hsp70 overexpression using gene transfer or heat stress, thus limiting its translational utility. A few compounds have been studied by various disciplines which, through their ability to inhibit Hsp90, can cause induction of Hsp70. The investigation of Hsp70-inducing pharmacological compounds has obvious clinical implications in terms of potential therapies to mitigate neuroinflammation and lead to neuroprotection from stroke or traumatic brain injury. This review will focus on the inflammation modulating properties of Hsp70, and the current literature surrounding the pharmacological induction in acute neurological injury models with comments on potential applications at the clinical level.
70kDa 热休克蛋白（Hsp70）被认为可以保护大脑免受各种损伤。尽管其机制在很大程度上仅限于其伴侣功能，但最近的研究表明 Hsp70 还可以调节炎症途径。脑损伤和缺血与主要是先天的免疫反应有关。Hsp70 似乎抑制了这种反应，从而导致神经功能的改善。然而，大多数此类研究都依赖于使用基因突变模型或通过基因转移或热应激过度表达 Hsp70，从而限制了其转化应用。一些化合物已被不同学科研究，它们通过抑制 Hsp90 的能力，可以诱导 Hsp70 的产生。研究 Hsp70 诱导的药理化合物在减轻神经炎症和防止中风或创伤性脑损伤引起的神经损伤方面具有明显的临床意义。本文综述了 Hsp70 的炎症调节特性，以及围绕急性神经损伤模型中 Hsp70 药理学诱导的最新文献，并对临床应用的潜在情况进行了评论。
