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Role of Heat Shock Proteins (HSP) in Neuroprotection for Ischemic Stroke

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Heat Shock Proteins in Neuroscience

Part of the book series: Heat Shock Proteins ((HESP,volume 20))

Abstract

Heat shock proteins (HSP) are upregulated early in response to many insults, including ischemic stroke. This upregulation allows cells to survive potentially lethal conditions via its chaperone functions which can assist in nascent protein folding and the prevention of protein aggregation. After ischemic stroke, HSP can directly interact with various proteins of the tightly regulated programmed cell death known as apoptosis. HSP70 also acts to modulate the inflammatory response following ischemic stroke. The 70 kDa inducible HSP also known as HSP70, has likely been the most extensively evaluated. HSP70 was shown to correlate to the phenomenon of induced tolerance. Studies in genetic mutant models or overexpression using gene transfer or heat stress, further showed that HSP70 led to improvements in brain cell survival. Pharmacological inducers of HSP70 demonstrated similar salutary effects in stroke models, and suggest that this approach has some translational value. Some of these pharmacological inducers have already been studied in humans for treatment of other conditions. Therefore, HSP seem to be neuroprotective, and should be further explored as a potential therapy against stroke and other neurodegenerative diseases.

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Abbreviations

17-AAG:

17-(Allylamino) geldanamycin

17-DMAG:

17-(2-dimethylaminoethyl) amino-17-demethoxygeldanamycin

AIF:

apoptosis inducing factor

Apaf-1:

apoptosis protease activating factor-1

AP-1:

activator portien-1

ATP:

adenosine triphosphate

BBB:

blood brain barrier

DIABLO/smac:

direct IAP-binding mitochondrial protein/second mitochondria-derived activator of caspases

GA:

geldanamycin

GGA:

geranylgeranylacetone

HO-1:

heme oxygenase-1

HSC:

heat shock cognate

HSF:

heat shock factor

HSP:

heat shock protein

smHSP:

small molecular HSP

IkB:

inhibitor of kappaB

IKK:

IkB kinase

IL-1:

interleukin-1

LOX-1:

low density lipoprotein receptor-1

NO:

nitric oxide

iNOS:

inducible nitric oxide synthase

JNK:

c-Jun N-terminal kinase

MCA:

middle cerebral artery

MMP:

matrix metalloproteinase

NADPH:

nicotinamide adenine dinucleotide phosphate

NF-kB:

nuclear factor-kappaB

iNOS:

inducible nitric oxide synthase

OGD:

oxygen glucose deprivation

PKB:

protein kinase B

ROS:

reactive oxygen species

STAT-1:

signal transducer and activator of transcription factor-1

TLR:

Toll-like receptor

TNF:

tumor necrosis factor

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Acknowledgments

This study was funded by grants from the National Institutes of Health (R01 NS 106441, RO3 NS101246), Department of Defense and the Veteran’s Merit Award (I01 BX000589) to MAY, Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03933017) to JYK and a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (NRF-2016M3C7A1905098) to JEL. Grants to MAY were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California.

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Authors and Affiliations

  1. Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea

    Jong Youl Kim, Meiying Huang & Jong Eun Lee

  2. BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

    Meiying Huang & Jong Eun Lee

  3. Department of Neurology, University of California, San Francisco, CA, USA

    Midori A. Yenari

  4. San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA

    Midori A. Yenari

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  1. Jong Youl Kim
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  2. Meiying Huang
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  3. Jong Eun Lee
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  4. Midori A. Yenari
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Corresponding authors

Correspondence to Jong Eun Lee or Midori A. Yenari .

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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Kim, J.Y., Huang, M., Lee, J.E., Yenari, M.A. (2019). Role of Heat Shock Proteins (HSP) in Neuroprotection for Ischemic Stroke. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Neuroscience. Heat Shock Proteins, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-030-24285-5_6

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