title: Anti-inflammatory properties and pharmacological induction of Hsp70 after brain injury.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kim
authors.forename: Jong Youl
authors.initials: JY
authors.lastname: Kim
authors.forename: Midori A
authors.initials: MA
authors.lastname: Yenari
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D006801:Humans
chemical_list: D000893:Anti-Inflammatory Agents; D018840:HSP70 Heat-Shock Proteins