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HSF1 Activation by Small Chemical Compounds for the Treatment of Neurodegenerative Diseases

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Heat Shock Factor

Abstract

Heat shock transcription factor 1 (HSF1) is a transcription factor that is activated upon the exposure of cells to various types of proteotoxic stress, such as heat shock stress and oxidative stress, which induces the expression of various molecular chaperones. HSF1-induced molecular chaperones, including heat shock protein 40 (Hsp40) and Hsp70, suppress protein misfolding through binding to structurally unstable proteins and thereby protect cells from proteotoxic stress. Therefore, activation of HSF1 is considered as a therapeutic approach against a group of neurodegenerative diseases that are caused by protein misfolding, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and the polyglutamine diseases. In fact, many compounds that activate HSF1 have been tested for their potential as therapeutic agents against neurodegenerative diseases. In this chapter, we introduce various HSF1-activating compounds, their mechanisms of activation of HSF1, and their therapeutic effects against neurodegenerative diseases.

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Acknowledgments

We thank Dr. H. Akiko Popiel (Tokyo Medical University) for editing the manuscript. We also thank lab members and Dr. Shigeomi Shimizu (Tokyo Medical and Dental University) for their helpful discussions. This work was supported, in part, by Grants-in-Aid for Scientific Research on Priority Areas (Research on Pathomechanisms of Brain Disorders, Protein Community, and Proteolysis) to Y.N. and on Innovative Areas (Synapse and Neurocircuit Pathology) to Y.N. and Strategic Research Program for Brain Sciences (Integrated research on neuropsychiatric disorders) to Y.N. from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; by Grants-in-Aid for Scientific Research (B) to Y.N. and (C) to N.F., for Challenging Exploratory Research to Y.N. and for Young Scientists (A) to T.T. from the Japan Society for the Promotion of Science, Japan; by Health and Labour Sciences Research Grants for Research on Development of New Drugs and Research on Measures for Intractable Diseases to Y.N. from the Ministry of Health, Labour, and Welfare, Japan; and by a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency to Y.N.

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Authors and Affiliations

  1. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan

    Nobuhiro Fujikake, Toshihide Takeuchi & Yoshitaka Nagai

  2. Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan

    Nobuhiro Fujikake

  3. Institute for Chemical Research, Kyoto University, Kyoto, 611-0011, Japan

    Toshihide Takeuchi

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  1. Nobuhiro Fujikake
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  2. Toshihide Takeuchi
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  3. Yoshitaka Nagai
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Correspondence to Nobuhiro Fujikake or Yoshitaka Nagai .

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  1. Department of Biochemistry & Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan

    Akira Nakai

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Fujikake, N., Takeuchi, T., Nagai, Y. (2016). HSF1 Activation by Small Chemical Compounds for the Treatment of Neurodegenerative Diseases. In: Nakai, A. (eds) Heat Shock Factor. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55852-1_14

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