Skip to main content
SpringerLink
Log in

Hsp70-Family Proteins and Neurodegenerative Diseases

  • Chapter
  • First Online:
HSP70 in Human Diseases and Disorders

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

Abstract

Neuronal proteostasis is a highly regulated and crucial component of neural function. Unlike other tissues and organ, cell loss due to damage and dysfunctional signaling mechanisms is not an option for the brain. Neurons are thusly dependent on the collective cellular machinery of the molecular chaperones. Hsp70, a molecular chaperone which hydrolyzes ATP to fold proteins into a functional state, has been implicated as both a driver of disease pathogenesis and a therapeutic target for the activities and associations identified in several neurodegenerative diseases. Through interaction studies, genetic models, and small molecule therapeutics which serve as chemical tools, we have gained a greater understanding and appreciation for the role of Hsp70 in several neurodegenerative diseases. This chapter will discuss the studies and tools which elucidated the role of Hsp70 family members in neurodegenerative disorders and will offer perspective into therapeutic interventions which may prove beneficial for treating these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

α-syn:

α-synuclein

Aß:

Amyloid beta

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BAG-1:

Bcl2-associated athanogene-1

CHIP:

c-terminus of Hsc70 interacting protein

CME:

Clatherin-mediated endocytosis

fALS:

Familial Amyotrophic lateral sclerosis

GA:

Geldanamycin

HD:

Huntington’s disease

Hsc:

Heat shock cognate

Hsp:

Heat shock protein

LRRK2:

Leucine-rich repeat kinase 2

MAPT, tau:

Microtubule associating protein tau

PCR:

Polymerase chain reaction

PD:

Parkinson’s disease

polyQ:

Polyglutamine-expansions

SCA:

Spinocerebellar ataxia

SNpc:

Substantia nigra pars compacta

SOD1:

Superoxide dismutase 1

TDP-43:

TAR DNA binding protein 43

UPS:

Ubiquitin-proteasome system

References

  • Abisambra, J., Jinwal, U. K., Miyata, Y., Rogers, J., Blair, L., Li, X., Seguin, S. P., Wang, L., Jin, Y., Bacon, J., et al. (2013). Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biological Psychiatry, 74, 367–374.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Al-Ramahi, I., Lam, Y. C., Chen, H. K., de Gouyon, B., Zhang, M., Perez, A. M., Branco, J., de Haro, M., Patterson, C., Zoghbi, H. Y., et al. (2006). CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. The Journal of Biological Chemistry, 281(36), 26714–26724.

    Article  PubMed  CAS  Google Scholar 

  • Aprile, F. A., Sormanni, P., & Vendruscolo, M. (2015). A rational design strategy for the selective activity enhancement of a molecular chaperone toward a target substrate. Biochemistry, 54, 5103–5112.

    Article  PubMed  CAS  Google Scholar 

  • Aprile, F. A., Kallstig, E., Limorenko, G., Vendruscolo, M., Ron, D., & Hansen, C. (2017). The molecular chaperones DNAJB6 and Hsp70 cooperate to suppress alpha-synuclein aggregation. Scientific Reports, 7, 9039.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Batulan, Z., Taylor, D. M., Aarons, R. J., Minotti, S., Doroudchi, M. M., Nalbantoglu, J., & Durham, H. D. (2006). Induction of multiple heat shock proteins and neuroprotection in a primary culture model of familial amyotrophic lateral sclerosis. Neurobiology of Disease, 24, 213–225.

    Article  PubMed  CAS  Google Scholar 

  • Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M., & Green, D. R. (2000). Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nature Cell Biology, 2, 469–475.

    Article  CAS  PubMed  Google Scholar 

  • Boluda, S., Iba, M., Zhang, B., Raible, K. M., Lee, V. M., & Trojanowski, J. Q. (2015). Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains. Acta Neuropathologica, 129, 221–237.

    Article  PubMed  CAS  Google Scholar 

  • Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., et al. (1997). ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron, 18, 327–338.

    Article  PubMed  CAS  Google Scholar 

  • Choi, J. S., Cho, S., Park, S. G., Park, B. C., & Lee, D. H. (2004). Co-chaperone CHIP associates with mutant Cu/Zn-superoxide dismutase proteins linked to familial amyotrophic lateral sclerosis and promotes their degradation by proteasomes. Biochemical and Biophysical Research Communications, 321, 574–583.

    Article  PubMed  CAS  Google Scholar 

  • Cummings, C. J., Mancini, M. A., Antalffy, B., DeFranco, D. B., Orr, H. T., & Zoghbi, H. Y. (1998). Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nature Genetics, 19, 148–154.

    Article  PubMed  CAS  Google Scholar 

  • Cummings, C. J., Sun, Y., Opal, P., Antalffy, B., Mestril, R., Orr, H. T., Dillmann, W. H., & Zoghbi, H. Y. (2001). Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Human Molecular Genetics, 10, 1511–1518.

    Article  PubMed  CAS  Google Scholar 

  • Dayalu, P., & Albin, R. L. (2015). Huntington disease: Pathogenesis and treatment. Neurologic Clinics, 33, 101–114.

    Article  PubMed  Google Scholar 

  • Dickey, C. A., Kamal, A., Lundgren, K., Klosak, N., Bailey, R. M., Dunmore, J., Ash, P., Shoraka, S., Zlatkovic, J., Eckman, C. B., et al. (2007). The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. The Journal of Clinical Investigation, 117, 648–658.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dickey, C. A., Koren, J., Zhang, Y. J., Xu, Y. F., Jinwal, U. K., Birnbaum, M. J., Monks, B., Sun, M., Cheng, J. Q., Patterson, C., et al. (2008). Akt and CHIP coregulate tau degradation through coordinated interactions. Proceedings of the National Academy of Sciences of the United States of America, 105, 3622–3627.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dou, F., Netzer, W. J., Tanemura, K., Li, F., Hartl, F. U., Takashima, A., Gouras, G. K., Greengard, P., & Xu, H. (2003). Chaperones increase association of tau protein with microtubules. Proceedings of the National Academy of Sciences of the United States of America, 100, 721–726.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Durham, H. D., Roy, J., Dong, L., & Figlewicz, D. A. (1997). Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS. Journal of Neuropathology and Experimental Neurology, 56, 523–530.

    Article  PubMed  CAS  Google Scholar 

  • Durr, A., Gargiulo, M., & Feingold, J. (2012). The presymptomatic phase of Huntington disease. Revue Neurologique (Paris), 168, 806–808.

    Article  CAS  Google Scholar 

  • Elliott, E., Tsvetkov, P., & Ginzburg, I. (2007). BAG-1 associates with Hsc70.Tau complex and regulates the proteasomal degradation of Tau protein. The Journal of Biological Chemistry, 282, 37276–37284.

    Article  PubMed  CAS  Google Scholar 

  • Evans, C. G., Jinwal, U. K., Makley, L. N., Dickey, C. A., & Gestwicki, J. E. (2011). Identification of dihydropyridines that reduce cellular tau levels. Chemical Communication (Cambridge), 47, 529–531.

    Article  CAS  Google Scholar 

  • Falsone, S. F., Kungl, A. J., Rek, A., Cappai, R., & Zangger, K. (2009). The molecular chaperone Hsp90 modulates intermediate steps of amyloid assembly of the Parkinson-related protein alpha-synuclein. The Journal of Biological Chemistry, 284, 31190–31199.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Flower, T. R., Chesnokova, L. S., Froelich, C. A., Dixon, C., & Witt, S. N. (2005). Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson’s disease. Journal of Molecular Biology, 351, 1081–1100.

    Article  PubMed  CAS  Google Scholar 

  • Fontaine, S. N., Zheng, D., Sabbagh, J. J., Martin, M. D., Chaput, D., Darling, A., Trotter, J. H., Stothert, A. R., Nordhues, B. A., Lussier, A., et al. (2016). DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. The EMBO Journal, 35, 1537–1549.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fukuzono, T., Pastuhov, S. I., Fukushima, O., Li, C., Hattori, A., Iemura, S., Natsume, T., Shibuya, H., Hanafusa, H., Matsumoto, K., et al. (2016). Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi. Genes to Cells, 21, 311–324.

    Article  PubMed  CAS  Google Scholar 

  • Gao, X., Carroni, M., Nussbaum-Krammer, C., Mogk, A., Nillegoda, N. B., Szlachcic, A., Guilbride, D. L., Saibil, H. R., Mayer, M. P., & Bukau, B. (2015). Human Hsp70 disaggregase reverses Parkinson’s-linked alpha-synuclein amyloid fibrils. Molecular Cell, 59, 781–793.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016). Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice. The Journal of Experimental Medicine, 213, 2635–2654.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iba, M., McBride, J. D., Guo, J. L., Zhang, B., Trojanowski, J. Q., & Lee, V. M. (2015). Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC’s afferent and efferent connections. Acta Neuropathologica, 130, 349–362.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ishigaki, S., Niwa, J., Yamada, S., Takahashi, M., Ito, T., Sone, J., Doyu, M., Urano, F., & Sobue, G. (2007). Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity. Neurobiology of Disease, 25, 331–341.

    Article  PubMed  CAS  Google Scholar 

  • Jana, N. R., Tanaka, M., Wang, G., & Nukina, N. (2000). Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: Their role in suppression of aggregation and cellular toxicity. Human Molecular Genetics, 9, 2009–2018.

    Article  PubMed  CAS  Google Scholar 

  • Jana, N. R., Dikshit, P., Goswami, A., Kotliarova, S., Murata, S., Tanaka, K., & Nukina, N. (2005). Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. The Journal of Biological Chemistry, 280, 11635–11640.

    Article  PubMed  CAS  Google Scholar 

  • Jankovic, J. (2008). Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery, and Psychiatry, 79, 368–376.

    Article  PubMed  CAS  Google Scholar 

  • Jinwal, U. K., Miyata, Y., Koren, J., 3rd, Jones, J. R., Trotter, J. H., Chang, L., O’Leary, J., Morgan, D., Lee, D. C., Shults, C. L., et al. (2009). Chemical manipulation of hsp70 ATPase activity regulates tau stability. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 29, 12079–12088.

    Article  CAS  Google Scholar 

  • Jinwal, U. K., O’Leary, J. C., 3rd, Borysov, S. I., Jones, J. R., Li, Q., Koren, J., 3rd, Abisambra, J. F., Vestal, G. D., Lawson, L. Y., Johnson, A. G., et al. (2010). Hsc70 rapidly engages tau after microtubule destabilization. The Journal of Biological Chemistry, 285, 16798–16805.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kalmar, B., Novoselov, S., Gray, A., Cheetham, M. E., Margulis, B., & Greensmith, L. (2008). Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1 mouse model of ALS. Journal of Neurochemistry, 107, 339–350.

    Article  PubMed  CAS  Google Scholar 

  • Kalmar, B., Edet-Amana, E., & Greensmith, L. (2012). Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis: Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases, 13, 378–392.

    Article  CAS  Google Scholar 

  • Kamal, A., Thao, L., Sensintaffar, J., Zhang, L., Boehm, M. F., Fritz, L. C., & Burrows, F. J. (2003). A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature, 425, 407–410.

    Article  CAS  PubMed  Google Scholar 

  • Kelly, E. B. (2013). Encyclopedia of human genetics and disease (Vol. 1). Santa Barbara: ABC-CLIO.

    Google Scholar 

  • Kieran, D., Kalmar, B., Dick, J. R., Riddoch-Contreras, J., Burnstock, G., & Greensmith, L. (2004). Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nature Medicine, 10, 402–405.

    Article  CAS  PubMed  Google Scholar 

  • Kiernan, M. C., Vucic, S., Cheah, B. C., Turner, M. R., Eisen, A., Hardiman, O., Burrell, J. R., & Zoing, M. C. (2011). Amyotrophic lateral sclerosis. Lancet, 377, 942–955.

    Article  CAS  PubMed  Google Scholar 

  • Klucken, J., Shin, Y., Hyman, B. T., & McLean, P. J. (2004). A single amino acid substitution differentiates Hsp70-dependent effects on alpha-synuclein degradation and toxicity. Biochemical and Biophysical Research Communications, 325, 367–373.

    Article  PubMed  CAS  Google Scholar 

  • Koren, J., 3rd, Jinwal, U. K., Jin, Y., O’Leary, J., Jones, J. R., Johnson, A. G., Blair, L. J., Abisambra, J. F., Chang, L., Miyata, Y., et al. (2010). Facilitating Akt clearance via manipulation of Hsp70 activity and levels. The Journal of Biological Chemistry, 285, 2498–2505.

    Article  PubMed  CAS  Google Scholar 

  • Koyama, S., Arawaka, S., Chang-Hong, R., Wada, M., Kawanami, T., Kurita, K., Kato, M., Nagai, M., Aoki, M., Itoyama, Y., et al. (2006). Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: Its modulation by the proteasome and Hsp70. Biochemical and Biophysical Research Communications, 343, 719–730.

    Article  PubMed  CAS  Google Scholar 

  • Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., & Lansbury, P. T., Jr. (2002). Alpha-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. Journal of Molecular Biology, 322, 1089–1102.

    Article  PubMed  CAS  Google Scholar 

  • Lichtenberg, M., Mansilla, A., Zecchini, V. R., Fleming, A., & Rubinsztein, D. C. (2011). The Parkinson’s disease protein LRRK2 impairs proteasome substrate clearance without affecting proteasome catalytic activity. Cell Death & Disease, 2, e196.

    Article  CAS  Google Scholar 

  • Liu, J., Shinobu, L. A., Ward, C. M., Young, D., & Cleveland, D. W. (2005). Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis. Journal of Neurochemistry, 93, 875–882.

    Article  PubMed  CAS  Google Scholar 

  • Lotz, G. P., Legleiter, J., Aron, R., Mitchell, E. J., Huang, S. Y., Ng, C., Glabe, C., Thompson, L. M., & Muchowski, P. J. (2010). Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. The Journal of Biological Chemistry, 285, 38183–38193.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luk, K. C., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2008). Interactions between Hsp70 and the hydrophobic core of alpha-synuclein inhibit fibril assembly. Biochemistry, 47, 12614–12625.

    Article  PubMed  CAS  Google Scholar 

  • McLean, P. J., Klucken, J., Shin, Y., & Hyman, B. T. (2004). Geldanamycin induces Hsp70 and prevents alpha-synuclein aggregation and toxicity in vitro. Biochemical and Biophysical Research Communications, 321, 665–669.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Muchowski, P. J., Schaffar, G., Sittler, A., Wanker, E. E., Hayer-Hartl, M. K., & Hartl, F. U. (2000). Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proceedings of the National Academy of Sciences of the United States of America, 97, 7841–7846.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Leary, J. C., 3rd, Li, Q., Marinec, P., Blair, L. J., Congdon, E. E., Johnson, A. G., Jinwal, U. K., Koren, J., 3rd, Jones, J. R., Kraft, C., et al. (2010). Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Molecular Neurodegeneration, 5, 45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Opazo, F., Krenz, A., Heermann, S., Schulz, J. B., & Falkenburger, B. H. (2008). Accumulation and clearance of alpha-synuclein aggregates demonstrated by time-lapse imaging. Journal of Neurochemistry, 106, 529–540.

    Article  PubMed  CAS  Google Scholar 

  • Orr, H. T. (2012). Cell biology of spinocerebellar ataxia. The Journal of Cell Biology, 197, 167–177.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park, S. H., Kukushkin, Y., Gupta, R., Chen, T., Konagai, A., Hipp, M. S., Hayer-Hartl, M., & Hartl, F. U. (2013). PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell, 154, 134–145.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O’Regan, J. P., Deng, H. X., et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 362, 59–62.

    Article  PubMed  CAS  Google Scholar 

  • Roy, J., Minotti, S., Dong, L., Figlewicz, D. A., & Durham, H. D. (1998). Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 18, 9673–9684.

    Article  CAS  Google Scholar 

  • Shimura, H., Schwartz, D., Gygi, S. P., & Kosik, K. S. (2004). CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. The Journal of Biological Chemistry, 279, 4869–4876.

    Article  CAS  PubMed  Google Scholar 

  • St Martin, J. L., Klucken, J., Outeiro, T. F., Nguyen, P., Keller-McGandy, C., Cantuti-Castelvetri, I., Grammatopoulos, T. N., Standaert, D. G., Hyman, B. T., & McLean, P. J. (2007). Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. Journal of Neurochemistry, 100, 1449–1457.

    PubMed  CAS  Google Scholar 

  • Tantucci, M., Mariucci, G., Taha, E., Spaccatini, C., Tozzi, A., Luchetti, E., Calabresi, P., & Ambrosini, M. V. (2009). Induction of heat shock protein 70 reduces the alteration of striatal electrical activity caused by mitochondrial impairment. Neuroscience, 163, 735–740.

    Article  PubMed  CAS  Google Scholar 

  • Tetzlaff, J. E., Putcha, P., Outeiro, T. F., Ivanov, A., Berezovska, O., Hyman, B. T., & McLean, P. J. (2008). CHIP targets toxic alpha-synuclein oligomers for degradation. The Journal of Biological Chemistry, 283, 17962–17968.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, A. D., Scaglione, K. M., Prensner, J., Gillies, A. T., Chinnaiyan, A., Paulson, H. L., Jinwal, U. K., Dickey, C. A., & Gestwicki, J. E. (2012). Analysis of the tau-associated proteome reveals that exchange of Hsp70 for Hsp90 is involved in tau degradation. ACS Chemical Biology, 7(10), 1677–1686.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Voss, K., Combs, B., Patterson, K. R., Binder, L. I., & Gamblin, T. C. (2012). Hsp70 alters tau function and aggregation in an isoform specific manner. Biochemistry, 51, 888–898.

    Article  PubMed  CAS  Google Scholar 

  • Warrick, J. M., Chan, H. Y., Gray-Board, G. L., Chai, Y., Paulson, H. L., & Bonini, N. M. (1999). Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genetics, 23, 425–428.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe, M., Dykes-Hoberg, M., Culotta, V. C., Price, D. L., Wong, P. C., & Rothstein, J. D. (2001). Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiology of Disease, 8, 933–941.

    Article  PubMed  CAS  Google Scholar 

  • Williams, A. J., Knutson, T. M., Colomer Gould, V. F., & Paulson, H. L. (2009). In vivo suppression of polyglutamine neurotoxicity by C-terminus of Hsp70-interacting protein (CHIP) supports an aggregation model of pathogenesis. Neurobiology of Disease, 33, 342–353.

    Article  PubMed  CAS  Google Scholar 

  • Witt, S. N. (2010). Hsp70 molecular chaperones and Parkinson’s disease. Biopolymers, 93, 218–228.

    Article  PubMed  CAS  Google Scholar 

  • Yoo, B. C., Seidl, R., Cairns, N., & Lubec, G. (1999). Heat-shock protein 70 levels in brain of patients with Down syndrome and Alzheimer’s disease. Journal of Neural Transmission. Supplementum, 57, 315–322.

    PubMed  CAS  Google Scholar 

  • Yu, A., Shibata, Y., Shah, B., Calamini, B., Lo, D. C., & Morimoto, R. I. (2014). Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition. Proceedings of the National Academy of Sciences of the United States of America, 111, E1481–E1490.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zarei, S., Carr, K., Reiley, L., Diaz, K., Guerra, O., Altamirano, P. F., Pagani, W., Lodin, D., Orozco, G., & Chinea, A. (2015). A comprehensive review of amyotrophic lateral sclerosis. Surgical Neurology International, 6, 171.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zetterstrom, P., Graffmo, K. S., Andersen, P. M., Brannstrom, T., & Marklund, S. L. (2011). Proteins that bind to misfolded mutant superoxide dismutase-1 in spinal cords from transgenic amyotrophic lateral sclerosis (ALS) model mice. The Journal of Biological Chemistry, 286, 20130–20136.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

This book chapter is dedicated to the life and memory of Dr. Chad A. Dickey. We apologize to the many authors who have contributed to our understanding of the molecular chaperone and neurodegenerative disease fields, and whose work we have failed to discuss or cite.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, College of Medicine, USF Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL, USA

    Zheying Sun, Roy J. Blackburn, Laura J. Blair & John Koren III

Authors
  1. Zheying Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roy J. Blackburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura J. Blair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Koren III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Koren III .

Editor information

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

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sun, Z., Blackburn, R.J., Blair, L.J., Koren, J. (2018). Hsp70-Family Proteins and Neurodegenerative Diseases. 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_2

Download citation

Publish with us

Policies and ethics

Search

Navigation