Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-09, Vol.9 (9), p.2020
• Main Authors: Kim, Jong Youl, Barua, Sumit, Huang, Mei Ying, Park, Joohyun, Yenari, Midori A, Lee, Jong Eun
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Animal models; Animals; Apoptosis; Benzoquinones - pharmacology; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain injuries; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - genetics; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Brain injury; Brain research; Cell death; Cell Death - drug effects; chaperone neuroprotection; Disease Models, Animal; Fatalities; Gene Expression Regulation; Gene transfer; Genes; Health aspects; heat shock protein 70; Heat shock proteins; Homeostasis; HSP70 Heat-Shock Proteins - agonists; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Hyperthermia; Inflammation; Kinases; Lactams, Macrocyclic - pharmacology; Nervous system; Neurological diseases; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - pharmacology; pharmacological induction; Physiological aspects; Protein Aggregates - drug effects; Protein folding; Protein Folding - drug effects; Protein interaction; Pyridines - pharmacology; Review; Signal transduction; Stroke; Transcription factors; Traumatic brain injury
• ISSN: 2073-4409; 2073-4409
• 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.