Targeted heat shock protein 72 for pulmonary cytoprotection

Ann N Y Acad Sci. 2016 Jun;1374(1):78-85. doi: 10.1111/nyas.13059. Epub 2016 May 6.

Abstract

Heat shock protein 72 (HSP72) is perhaps the most important member of the HSP70 family of proteins, given that it is induced in a wide variety of tissues and cells to combat stress, particularly oxidative stress. Here, we review independent observations of the critical role this protein plays as a pulmonary cytoprotectant and discuss the merits of developing HSP72 as a therapeutic for rapid delivery to cells and tissues after a traumatic event. We also discuss the fusion of HSP72 to a cell-penetrating single-chain Fv antibody fragment derived from mAb 3E10, referred to as Fv-HSP70. This fusion construct has been validated in vivo in a cerebral infarction model and is currently in testing as a clinical therapeutic to treat ischemic events and as a fieldable medical countermeasure to treat inhalation of toxicants caused by terrorist actions or industrial accidents.

Keywords: HSP70; HSP72; apoptosis inhibitor; medical countermeasure; oxidative stress; reperfusion therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytoprotection*
  • HSP72 Heat-Shock Proteins / genetics
  • HSP72 Heat-Shock Proteins / metabolism*
  • Humans
  • Lung / cytology*
  • Lung / metabolism*
  • Models, Biological
  • Molecular Targeted Therapy*
  • Stress, Physiological

Substances

  • HSP72 Heat-Shock Proteins