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Heat Shock Protein70 in Neurological Disease

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HSP70 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 14))

Abstract

The HSP70 is a chaperon protein that is expressed during stress conditions that participates in many biological processes, including protein trafficking, nascent polypeptide folding and the refolding of the wrong proteins and cleaning of the misfolded ones. The expression is increased during various pathological conditions such as cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. They are found in both intracellular and extracellular compartments. HSP70 exhibits different functions in accordance with its location. Intracellular HSP70 exerts cytoprotective functions as a chaperone protein, whereas extracellular HSP70 exerts immunomodulatory functions that trigger immunological responses. They play an auxiliary role in antigen presentation in the appearance of immunological response in multiple sclerosis. Epilepsy is thought to have emerged as a stressor. HSP overexpression is proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. In this chapter, we wanted to summarize the recent studies on the role of HSP70 in neurological disorders.

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Abbreviations

Aβ:

Amiloid beta

ALS:

Amyotrophic Lateral Sclerosis

CJD:

Creutzfeldt-Jakob disease

DA:

Dopamine

EAE:

Experimental allegic encephalomyelitis

FFI:

Fatal familial insomnia

GSS:

Gerstmann-Sträussler-Scheinker syndrome

HD:

Huntington disease

HSP:

Heat shock protein

LRRK2:

Leucine-rich repeat kinase-2

MG:

Myasthenia gravis

MS:

Multiple sclerosis

MTS:

Mesial temporal sclerosis

PD:

Parkinson’s disease

PINK1:

PTEN-induced putative kinase 1

polyQ:

Poly-glutamine

PrPC:

Cellular prion associated proteins

PrPSc:

Disease associated prion proteins

SNCA:

Alpha-synuclein

TDP-43:

Tar DNA binding protein 43

UPS:

Ubiquitin-proteasome system

vCJD:

Variant Creutzfeldt-Jakob disease

References

  • Ahmad, A. (2010). DnaK/DnaJ/GrpE of HSP70 system have differing effects on alpha-synuclein fibrillation involved in Parkinson’s disease. International Journal of Biological Macromolecules, 46(2), 275–279.

    Article  CAS  PubMed  Google Scholar 

  • Ammon-Treiber, S., Grecksch, G., Angelidis, C., et al. (2007). Pentylenetetrazol kindling in mice overexpressing heat shock protein 70. Naunyn-Schmiedeberg’s Arch Pharmacol, 375, 115–112.

    Article  CAS  Google Scholar 

  • Auluck, P. K., Chan, H. Y., Trojanowski, J. Q., et al. (2002). Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science, 295(5556), 865–868.

    Article  CAS  PubMed  Google Scholar 

  • Bersuker, K., Hipp, M. S., Calamini, B., et al. (2013). Heat shock response activation exacerbates inclusion body formation in a cellular model of Huntington disease. The Journal of Biological Chemistry, 288, 23633–23638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boiocchi, C., Monti, M. C., Osera, C., et al. (2016). Heat shock protein 70-hom gene polymorphism and protein expression in multiple sclerosis. Journal of Neuroimmunology, 298, 189–193.

    Article  CAS  PubMed  Google Scholar 

  • Budka, H. (2003). Neuropathology of prion diseases. British Medical Bulletin, 66, 121–130.

    Article  CAS  PubMed  Google Scholar 

  • Cassu, D., Masala, S., Frau, J., et al. (2013). Anti Mycobacterium avium subsp. Paratuberculosis heat shock protein 70 antibodies in sera of Sardinian patients with multiple sclerosis. Journal of the Neurological Sciences, 355(1–2), 131–133.

    Article  CAS  Google Scholar 

  • Chen, S., & Brown, I. R. (2007). Neuronal expression of constitutive heat shock proteins: Implications for neurodegenerative diseases. Cell Stress & Chaperones, 12(1), 51–58.

    Article  CAS  Google Scholar 

  • Chiba, S., Yokota, S., Yonekura, K., et al. (2006). Autoantibodies against HSP70 family proteins were detected in the cerebrospinal fluid from patients with multiple sclerosis. Journal of the Neurological Sciences, 241(1–2), 39–43.

    Article  CAS  PubMed  Google Scholar 

  • Ciechanover, A., & Kwon, Y. T. (2015). Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies. Experimental & Molecular Medicine, 47, 147.

    Article  CAS  Google Scholar 

  • Coban, P., Çe, P., Erkizan, O., & Gedizlioglu, M. (2011). Heat shock protein 27 in migraine patients. Journal of Neurological Sciences [Turkish], 28(1), 28–34.

    Google Scholar 

  • Davies, S. W., Turmaine, M., Cozens, B. A., et al. (1997). Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90(3), 537–548.

    Article  CAS  PubMed  Google Scholar 

  • Davies, S. W., Beardsall, K., Turmaine, M., et al. (1998). Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions? Lancet, 351, 131.

    Article  CAS  PubMed  Google Scholar 

  • Desler, C., Lillenes, M. S., Tønjum, T., et al. (2017). The role of mitochondrial dysfunction in the progression of Alzheimer’s disease. Current Medicinal Chemistry. https://doi.org/10.2174/0929867324666170616110111. [Epub ahead of print].

  • Diedrich, J. F., Carp, R. I., & Haase, A. T. (1993). Increased expression of heat shock protein, transferrin, and beta 2-microglobulin in astrocytes during scrapie. Microbial Pathogenesis, 15, 1–6.

    Article  CAS  PubMed  Google Scholar 

  • Fiszer, U., Fredrikson, S., & Członkowska, A. (1996). Humoral response to HSP 65 and HSP 70 in cerebrospinal fluid in Parkinson’s disease. Journal of the Neurological Sciences, 139(1), 66–70.

    Article  CAS  PubMed  Google Scholar 

  • Gómez-Chocoa, M., Doucerain, C., Urra, X., et al. (2014). Presence of heat shock protein 70 in secondary lymphoid tissue correlates with stroke prognosis. Journal of Neuroimmunology, 270(1–2), 67–74.

    Article  CAS  Google Scholar 

  • Halliday, G. M., Holton, J. L., Revesz, T., et al. (2011). Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathologica, 122, 187–204.

    Article  CAS  PubMed  Google Scholar 

  • Helgeland, G., Petzold, A., Hoff, J. M., et al. (2010). Anti-heat shock protein 70 antibody levels are increased in myasthenia gravis and Guillain-Barré syndrome. Journal of Neuroimmunology, 225(1–2), 180–183.

    Article  CAS  PubMed  Google Scholar 

  • Hernández-Pedro, N. Y., Espinosa-Ramirez, G., de la Cruz, V. P., et al. (2013). Initial immunopathogenesis of multiple sclerosis: Innate immune response. Clinical and Developmental Immunology. Article ID 413465, 15 pages.

    Google Scholar 

  • Ho, A. K., & Hocaoglu, M. B. (2011). Impact of Huntington’s across the entire disease spectrum: The phases and stages of disease from the patient perspective. Clinical Genetics, 80(3), 235–239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho, S. L., Poon, C. Y., Lin, C., et al. (2015). Inhibition of β-amyloid aggregation By albiflorin, aloeemodin and neohesperidin and their neuroprotective effect on primary hippocampal cells against β-amyloid induced toxicity. Current Alzheimer Research, 12(5), 424–433.

    Article  CAS  PubMed  Google Scholar 

  • Huang, C., Cheng, H., Hao, S., et al. (2006). Heat shock protein 70 inhibits alpha-synuclein fibril formation via interactions with diverseintermediates. Journal of Molecular Biology, 364(3), 323–336.

    Article  CAS  PubMed  Google Scholar 

  • Hung, S. Y., & Fu, W. M. (2017). Drug candidates in clinical trials for Alzheimer’s disease. Biomedical Science, 24(1), 47.

    Article  Google Scholar 

  • Huntington, G. (1872). Med Surg Report 26, 320.

    Google Scholar 

  • Jones, G., Song, Y., Chung, S., et al. (2004). Propagation of Saccharomyces cerevisiae [PSI+] prion is impaired by factors that regulate HSP70 substrate binding. Molecular and Cellular Biology, 24(9), 3928–3937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kacimi, R., & Yenari, M. A. (2015). Pharmacologic heat shock protein 70 induction confers cytoprotection against inflammation in gliovascular cells. Glia, 63(7), 1200–1212.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalmar, B., & Greensmith, L. (2017). Cellular chaperones as therapeutic targets in ALS to restore protein homeostasis and improve cellular function. Frontiers in Molecular Neuroscience, 10, 251. https://doi.org/10.3389/fnmol.2017.00251.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kandratavicius, L., Hallak, J. E., Carlotti, C. G., et al. (2014). Hippocampal expression of heat shock proteins in mesial temporal lobe epilepsy with psychiatric comorbidities and their relation to seizure outcome. Epilepsia, 55, 1834–1843.

    Article  CAS  PubMed  Google Scholar 

  • Kazemi-Esfarjani, P., & Benzer, S. (2002). Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1. Human Molecular Genetics, 11(21), 2657–2672.

    Article  CAS  PubMed  Google Scholar 

  • Kenward, N., Hope, J., Landon, M., et al. (1994). Expression of polyubiquitin and heat-shock protein 70 genes increases in the later stages of disease progression in scrapie-infected mouse brain. Journal of Neurochemistry, 62, 1870–1877.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J. Y., Kim, N., Zheng, Z., et al. (2016). 70kDa heat shock protein downregulates dynamin in experimental stroke: A new therapeutic target? Stroke, 47(8), 2003–2011.

    Article  CAS  Google Scholar 

  • King, C. Y., Tittmann, P., Gross, H., et al. (1997). Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. Proceedings of the National Academy of Sciences of the United States of America, 94(13), 6618–6622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klucken, J., Shin, Y., Masliah, E., et al. (2004). HSP70 reduces alpha-synuclein aggregation and toxicity. The Journal of Biological Chemistry, 279(24), 25497–25502.

    Article  CAS  PubMed  Google Scholar 

  • Krüger, R., Kuhn, W., Müller, T., et al. (1998). Ala30Pro mutation in the gene encoding alpha synuclein in Parkinson’s disease. Nature Genetics, 18(2), 106–108.

    Article  PubMed  Google Scholar 

  • Lu, R. C., Tan, M. S., Wang, H., et al. (2014). Heat shock protein 70 in Alzheimer’s disease. BioMed Research International, 2014, 435203. https://doi.org/10.1155/2014.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lucchinetti, C., Brück, W., Parisi, J., et al. (2000). Heterogenity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Annals of Neurology, 47(6), 707–717.

    Article  CAS  PubMed  Google Scholar 

  • Mansilla, M. J., Costa, C., Eixarch, H., et al. (2014). HSP70 regulates immune response in experimental autoimmune encephalomyelitis. PLoS One, 9(8). https://doi.org/10.1371/journal.pone.0105737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monsellier, E., Redeker, V., Ruiz-Arlandis, G., et al. (2015). Molecular interaction between the chaperone Hsc70 and the N-terminal flank of huntingtin exon 1 modulates aggregation. The Journal of Biological Chemistry, 290(5), 2560–2576.

    Article  CAS  PubMed  Google Scholar 

  • Muchowski, P. J., & Wacker, J. L. (2005). Modulation of neurodegeneration by molecular chaperones. Nature Reviews. Neuroscience, 6(1), 11–22.

    Article  CAS  PubMed  Google Scholar 

  • Munakata, S., Chen, M., Aosai, F., et al. (2008). The clinical significance of anti-heat shock cognate protein 71 antibody in myasthenia gravis. Journal of Clinical Neuroscience, 15(2), 158–165.

    Article  CAS  PubMed  Google Scholar 

  • Namba, Y., Tomonaga, M., Ohtsuka, K., et al. (1991). HSP 70 is associated with abnormal cytoplasmic inclusions characteristic of neurodegenerative diseases. Nō to Shinkei, 43(1), 57–60.

    PubMed  CAS  Google Scholar 

  • Patterson, K. R., Ward, S. M., Combs, B., et al. (2011). Heat shock protein 70 prevents both tau aggregation and the inhibitory effects of preexisting tau aggregates on fast axonal transport. Biochemistry, 50(47), 10300–10310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pratt, W. B., Gestwicki, J. E., Osawa, Y., et al. (2015). Targeting proteostasis through the protein quality control function of the HSP90/HSP70-based chaperone machinery for treatment of adult onset neurodegenerative diseases. Annual Review of Pharmacology and Toxicology, 55, 353–371.

    Article  CAS  PubMed  Google Scholar 

  • Prusiner, S. B. (2001). Shattucklecture – neurodegenerative diseases and prions. The New England Journal of Medicine, 344(20), 1516–1526.

    Article  CAS  PubMed  Google Scholar 

  • Roodveldt, C., Bertoncini, C. W., Andersson, A., et al. (2009). Chaperone proteostasis in Parkinson’s disease: Stabilization of the HSP70/alpha-synuclein complex by Hip. The EMBO Journal, 28(23), 3758–3770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabirzhanov, B., Stoica, B. A., Hanscom, M., et al. (2012). Over-expression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis. Journal of Neurochemistry, 123(4), 542–554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selmaj, K., Brosnan, C. F., & Raine, C. S. (1991). Immunology. Proceedings of the National Academy of Sciences of the United States of America, 88, 6452–6456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shevtsov, M. A., Nikolaev, B. P., Yakovleva, L. Y., et al. (2014). Neurotherapeutic activity of the recombinant heat shock protein HSP70 in a model of focal cerebral ischemia in rats. Drug Design Development and Therapy, 8, 639–650.

    Article  CAS  Google Scholar 

  • Suhr, S. T., Senut, M. C., Whitelegge, J. P., et al. (2001). Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. The Journal of Cell Biology, 153(2), 283–294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tagawa, K., Marubuchi, S., Qi, M. L., et al. (2007). The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. The Journal of Neuroscience, 27(4), 868–880.

    Article  CAS  PubMed  Google Scholar 

  • Talla, V., Porciatti, V., Chiodo, V., et al. (2014). Gene therapy with mitochondrial heat shock protein 70 suppresses visual loss and optic atrophy in experimental autoimmune encephalomyelitis. Investigative Ophthalmology & Visual Science, 55(8), 5214–5226.

    Article  CAS  Google Scholar 

  • Tamguney, G., Giles, K., Glidden, D. V., et al. (2008). Genes contributing to prion pathogenesis. The Journal of General Virology, 89, 1777–1788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vonsattel, J. P., & DiFiglia, M. (1998). Huntington disease. Journal of Neuropathology and Experimental Neurology, 57(5), 369–384.

    Article  CAS  PubMed  Google Scholar 

  • Whyte, L. S., Lau, A. A., Hemsley, K. M., et al. (2017). Endo-lysosomal and autophagic dysfunction: A driving factor in Alzheimer’s disease? Neurochemistry, 140(5), 703–717.

    Article  CAS  Google Scholar 

  • Yon, M. I., Titiz, A. P., Bilen, S., et al. (2016). Elevated interictal serum HSP-70 levels as an indicator of neurodegeneration for chronic migraine. The Journal of the Pakistan Medical Association, 66(6), 677–681.

    PubMed  Google Scholar 

  • Zhou, Y., Gu, G., Goodlett, D. R., et al. (2004). Analysis of alpha-synuclein-associated proteins by quantitative proteomics. The Journal of Biological Chemistry, 279(37), 39155–39164.

    Article  CAS  PubMed  Google Scholar 

  • Zoghbi, H. Y., & Orr, H. T. (2000). Glutamine repeats and neurodegeneration. Annual Review of Neuroscience, 23, 217–247.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the editorial staff for the opportunity of being able to be among the authors of the book.

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Authors and Affiliations

  1. Division of Neurology, SB University, Izmir Bozyaka Training and Research Hospital, Alsancak Izmir, Turkey

    Pinar Ortan

  2. Division of İnternal Medicine, SB University, Izmir Bozyaka Training and Research Hospital, Bornova Izmir, Turkey

    Ozden Yildirim Akan

  3. Division of Physiology, Dokuz Eylul University Medical Faculty, Inciralti/Izmir, Turkey

    Ferda Hosgorler

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  1. Pinar Ortan
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  2. Ozden Yildirim Akan
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Editors and Affiliations

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

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Punit Kaur

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Ortan, P., Akan, O.Y., Hosgorler, F. (2018). Heat Shock Protein70 in Neurological Disease. In: Asea, A., Kaur, P. (eds) HSP70 in Human Diseases and Disorders. Heat Shock Proteins, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-89551-2_3

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