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Neuroprotection of Heat Shock Proteins (HSPs) in Brain Ischemia

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Translational Research in Stroke

Part of the book series: Translational Medicine Research ((TRAMERE))

Abstract

Heat shock proteins (HSPs) were among the first early genes recognized to be upregulated following brain ischemia. This upregulation was thought to be part of an endogenous response to stress, but the significance of these proteins was not fully understood until genetic manipulation to overexpress or delete these genes showed that they indeed participated in the prevention of cell death. The mechanisms by which HSPs prevent cell death are multifold. In addition to their chaperone properties where they can assist in nascent protein folding and the prevention of protein aggregation, HSPs seem to also participate in specific cell death pathways and inflammation. The most studied of these proteins is the 70 kDa inducible HSP also known as HSP70. The availability of a few pharmacological inducers has shown that this same neuroprotective effect can be recapitulated in wildtype animal models. Further, some of these inducers have already been studied in humans for treatment of other conditions. HSPs should be further investigated for their translational relevance in the treatment of stroke and related conditions.

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Abbreviations

17-AAG:

17-(Allylamino)geldanamycin

AIF:

Apoptosis-inducing factor

Apaf-1:

Apoptosis protease activating factor-1

ATP:

Adenosine triphosphate

BBB:

Blood-brain barrier

DIABLO/smac:

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

HO-1:

Heme oxygenase-1

HSC:

Heat shock cognate

HSE:

Heat shock element

HSF:

Heat shock factor

HSP:

Heat shock protein

IkB:

Inhibitor of kappaB

IKK:

IkB kinase

IL-1:

Interleukin-1

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

NOS:

Nitric oxide synthase

OGD:

Oxygen glucose deprivation

PKB:

Protein kinase B

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 (RO1 NS40516), 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 (N12F) grant funded by the Korea government (MEST) (NRF-2017R1A2B2005350) 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, 03722, Republic of Korea

    Jong Youl Kim & Jong Eun Lee

  2. BK21 Plus Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Jong Eun Lee

  3. Department of Neurology, University of California, San Francisco & the San Francisco Veterans Affairs Medical Center, Neurology (127) VAMC 4150 Clement St., San Francisco, CA, USA

    Midori A. Yenari

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  1. Jong Youl Kim
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  2. Jong Eun Lee
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  3. Midori A. Yenari
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Correspondence to Midori A. Yenari .

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Editors and Affiliations

  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, California, USA

    Paul A. Lapchak

  2. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Guo-Yuan Yang

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Kim, J.Y., Lee, J.E., Yenari, M.A. (2017). Neuroprotection of Heat Shock Proteins (HSPs) in Brain Ischemia. In: Lapchak, P., Yang, GY. (eds) Translational Research in Stroke. Translational Medicine Research. Springer, Singapore. https://doi.org/10.1007/978-981-10-5804-2_17

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