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The Role of Heat Shock Proteins during Neurodegeneration in Alzheimer’s, Parkinson’s and Huntington’s Disease

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Heat Shock Proteins in Neural Cells

Part of the book series: Neuroscience Intelligence Unit ((NIU.LANDES))

Abstract

A number of acute and chronic neurodegenerative conditions are associated by protein misfolding and aggregation of proteins within and outside cells. Misfolded proteins and protein aggregation are controlled by molecular chaperones such as heat shock proteins (HSPs) that are constitutively and inducibly expressed in the nervous system. There is increasing evidence that HSPs could counteract common pathological mechanisms that take place during Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). This is achieved by HSPs either interfering with the misfolded disease proteins preventing unwanted interactions with other cellular proteins and/or by reducing the risk of formation of toxic oligomeric assemblies of the respective disease proteins such as tau and amyloid-β in AD, α-synuclein in PD and huntingtin in HD. But HSPs are also expected to interfere with detrimental processes that occur during these diseases including oxidative stress and abnormal activation of signaling pathways or act supportive towards degradation systems such as the ubiquitin proteasome- and the autophagic-lysosomal pathway. Specific neuronal structures such as synapses and axons also harbour HSPs that may be misregulated during the disease process. Hence HSPs are expected to be critically involved in the progression of AD, PD and HD making them potential therapeutic targets and the studies discussed in this chapter support this view.

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References

  1. Selkoe DJ. Cell biology of protein misfolding: The examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 2004; 6(11):1054–61.

    Article  CAS  PubMed  Google Scholar 

  2. Hartle FU. Molecular chaperones in cellular protein folding. Nature 1996; 381:571–579.

    Article  Google Scholar 

  3. Walsh DM, Selkoe DJ. Oligomers on the brain: The emerging role of soluble protein aggregates in neurodegeneration. Protein and Pept Lett 2004; 11(3):1–16.

    Article  Google Scholar 

  4. Goedert M. Tau protein and neurodegeneration. Semin Cell Dev Biol 2004; 15(1):45–49.

    Article  CAS  PubMed  Google Scholar 

  5. Drewes G. MARKing tau for tangles and toxicity. Trends Biochem Sci 2004; 29(10):548.

    Article  CAS  PubMed  Google Scholar 

  6. Lee MY, Giasson BI, Trojanowski JQ. More than just two peas in a pod: Common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases. Trends Neurosci 2004; 27(3):129–133.

    Article  CAS  PubMed  Google Scholar 

  7. Magrane J, Smith RC, Walsh K et al. Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons. J Neurosci 2004; 24(7):1700–1706.

    Article  CAS  PubMed  Google Scholar 

  8. Rochet JC, Outeiro TF, Conway KA et al. Interactions among alpha-synuclein, dopamine, and biomembranes. J Mol Neurosci 2004; 23:23–33.

    Article  CAS  PubMed  Google Scholar 

  9. Healy DG, Abou-Sleiman PM, Wood NW. PINK, PANK, or PARK? A clinicians’s guide to familial parkinsonism. The Lancet 2004; 3:652–662.

    Article  CAS  Google Scholar 

  10. Zoghbi HY, Orr HT. Glutamine repeats and neurodegeneration. Ann Rev Neurosci 2000; 23:217–247.

    Article  CAS  PubMed  Google Scholar 

  11. Davies SW, Turmaine M, Cozens BA et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997; 90(3):537–548.

    Article  CAS  PubMed  Google Scholar 

  12. Perutz MF. Glutamine repeats and neurodegenerative diseases: Molecular aspects. Trends Biochem Sci 1999; 24(2):58–63.

    Article  CAS  PubMed  Google Scholar 

  13. Wyttenbach A. Role of heat shock proteins during polyglutamine neurodegeneration: Mechanisms and hypothesis. J Mol Neurosci 2004; 23(1–2):69–96.

    Article  CAS  PubMed  Google Scholar 

  14. Shimura H, Miura-Shimura Y, Kosik K. Binding of tau to heat shock protein 27 leads to decreased concentration of hyperphosphorylated tau and enhanced cell survival. J Biol Chem 2004; 279(17):17957–17962.

    Article  CAS  PubMed  Google Scholar 

  15. Dedmon MM, Christodoulou J, Wilson MR et al. Heat shock protein 70 inhibits alpha-synuclein fibril formation via preferential binding to prefibrillar species. J Biol Chem 2005; 280(15):14733–14740.

    Article  CAS  PubMed  Google Scholar 

  16. Schaffar G, Breuer P, Boteva R et al. Cellular toxicity of polyglutamine expansion proteins: Mechanism of transcription factor deactivation. Mol Cell 2004; 15(1):95–105.

    Article  CAS  PubMed  Google Scholar 

  17. Dou F, Netzer WJ, Tanemura K et al. Chaperones increase association of tau protein with microtubules. Proc Natl Acad Sci USA 2003; 100(2):721–726.

    Article  CAS  PubMed  Google Scholar 

  18. Yang Y, Turner RS, Gaut JR. The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Abeta40 and Abeta42 secretion. J Biol Chem 1998; 273:25552–25555.

    Article  CAS  PubMed  Google Scholar 

  19. Furlong RA, Narain Y, Rankin J et al. Alpha-synuclein overexpression promotes aggregation of mutant huntingtin. Biochem J 2000; 346(3):577–581.

    Article  CAS  PubMed  Google Scholar 

  20. Charles V, Mezey E, Reddy PH et al. Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington’s disease patients and transgenic mouse models. Neurosci Lett 2000; 289(1):29–32.

    Article  CAS  PubMed  Google Scholar 

  21. Kim S, Nollen EA, Kitagawa K et al. Polyglutamine protein aggregates are dynamic. Nat Cell Biol 2002; 4(10):826–831.

    Article  CAS  PubMed  Google Scholar 

  22. Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 2005; 6:11–22.

    Article  CAS  PubMed  Google Scholar 

  23. Andersen JK. Oxidative stress in neurodegeneration: Cause or consequence? Nat Rev Neurosci 2004; 10:S18–25.

    Article  Google Scholar 

  24. Browne SE, Ferrante RJ, Beal MF. Oxidative stress in Huntington’s disease. Brain Pathol 1999; 9:147–163.

    CAS  PubMed  Google Scholar 

  25. Tabrizi SJ, Workman J, Hart PE et al. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol 2000; 47(1):80–86.

    Article  CAS  PubMed  Google Scholar 

  26. Wyttenbach A, Sauvageot O, Carmichael J et al. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum Mol Genet 2002; 11(9):1137–1151.

    Article  CAS  PubMed  Google Scholar 

  27. Mattson MP. Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann NY Acad Sci 2004; 1012:37–50.

    Article  CAS  PubMed  Google Scholar 

  28. Tabner BJ, Turnbull S, El-Agnaf OM et al. Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease. Free Radic Biol Med 2002; 32(11):1076–1083.

    Article  CAS  PubMed  Google Scholar 

  29. Arrigo AP, Virot S, Chaufour S et al. Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Sigal 2005; 7(3–4):414–422.

    Article  CAS  Google Scholar 

  30. Tatton W, Chalmers-Redman R, Brown D et al. Apoptosis in Parkinson’s Disease: Signals for Neruonal Degradation. Ann Neurol 2003; 53(3):61–72.

    Article  CAS  Google Scholar 

  31. Takuma K, Yan SS, Stern DM et al. Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer’s disease. J Pharmacol Sci 2005; 97(3):312–316.

    Article  CAS  PubMed  Google Scholar 

  32. Hickey MA, Chesselet MF. Apoptosis in Huntington’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27(2):255–265.

    Article  CAS  PubMed  Google Scholar 

  33. Beere HM. Stressed to death: Regulation of apoptotic signaling pathways by the heat shock proteins. Sci STKE 2001; 93:RE1.

    Google Scholar 

  34. Kadowaki H, Nishitoh H, Ichijo H. Survival and apoptosis in ER stress: The role of protein kinases. J Chem Neuroanat 2004; 28(1–2):93–100.

    CAS  PubMed  Google Scholar 

  35. Kouroku Y, Fujita E, Jimbo A et al. Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation. Hum Mol Genet 2002; 11(13):1505–1515.

    Article  CAS  PubMed  Google Scholar 

  36. Harper SJ, Wilkie N. MAPKs: New targets for neurodegeneration. Expert Opin Ther Targets 2003; 7(2):187–200.

    Article  CAS  PubMed  Google Scholar 

  37. Bell KA, O’Riordan KJ, Sweatt JD et al. MAPK recruitment by beta-amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time. J Neurochem 2004; 91:349–361.

    Article  CAS  PubMed  Google Scholar 

  38. Ross CA, Pickart CM. The ubiquitin-proteasome pathway in Parkinson’s disease and other neurodegenerative diseases. Trends Cell Biol 2004; 14(12):703–711.

    Article  CAS  PubMed  Google Scholar 

  39. Donaldson KM, Li W, Ching KA et al. Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci USA 2003; 100(15):8892–8897.

    Article  CAS  PubMed  Google Scholar 

  40. Chen S, Berthelier V, Yang W et al. Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity. J Mol Biol 2001; 311:173–182.

    Article  CAS  PubMed  Google Scholar 

  41. Lashuel HA, Hartley D, Petre BM et al. Mixtures of wild-type and a pathogenic (E22G) form of Ab40 in vitro accumulate protofibrils, including amyloid pores. J Mol Biol 2003; 332:795–808.

    Article  CAS  PubMed  Google Scholar 

  42. Monoi H, Futaki S, Kugimiya S et al. Poly-L-glutamine forms cation channels: Relevance to the pathogenesis of the polyglutamine diseases. Biophys J 2000; 78(6):2892–2899.

    Article  CAS  PubMed  Google Scholar 

  43. Kourie JI, Henry CL. Ion channel formation and membrane-linked pathologies of misfolded hydrophobic proteins: The role of dangerous unchaperoned molecules. Clin Exp Pharmacol Physiol 2002; 29:741–753.

    Article  CAS  PubMed  Google Scholar 

  44. Kegel KB, Sapp E, Yoder JL et al. Huntingtin associates with membranes by directly binding phospholipids. Washington, DC: Society for Neuroscience, 2004:445.17, (Abstract).

    Google Scholar 

  45. Snyder H, Mensah K, Theisler C et al. Aggregated and monomeric alpha-synuclein bind to the S6’ proteasomal protein and inhibit proteasomal function. J Biol Chem 2003; 278(14):11753–9.

    Article  CAS  PubMed  Google Scholar 

  46. Cuervo AM, Stefanis L, Fredenburg R et al. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 2004; 305(5688):1292–5.

    Article  CAS  PubMed  Google Scholar 

  47. Keck S, Nitsch R, Grune T et al. Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer’s disease. J Neurochem 2003; 85(1):115–122.

    Article  CAS  PubMed  Google Scholar 

  48. Nixon RA, Cataldo AM, Mathews PM. The endosomal-lysosomal system of neurons in Alzheimer’s disease pathogenesis: A review. Neurochem Res 2000; 25(9–10):1161–72.

    Article  CAS  PubMed  Google Scholar 

  49. Wyttenbach A, Carmichael J, Swartz J et al. Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington’s disease. Proc Natl Acad Sci USA 2000; 97(6):2898–2903.

    Article  CAS  PubMed  Google Scholar 

  50. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2000; 292(5521):1552–2.

    Article  Google Scholar 

  51. Venkatraman P, Wetzel R, Tanaka M et al. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol Cell 2004; 14(1):95–104.

    Article  CAS  PubMed  Google Scholar 

  52. Ravikumar B, Vacher C, Berger Z et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 2004; 36(6):585–595.

    Article  CAS  PubMed  Google Scholar 

  53. Jana NR, Dikshit P, Goswami A et al. Cochaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J Biol Chem 2005; 280(12):11635–40.

    Article  CAS  PubMed  Google Scholar 

  54. Parcellier A, Schmitt E, Gurbuxani S et al. HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation. Mol Cell Biol 2003; 23(16):5790–5802.

    Article  CAS  PubMed  Google Scholar 

  55. Li JY, Plomann M, P B. Huntington’s disease: A synaptopathy? Trends Mol Med 2003; 9(10):414–420.

    Article  CAS  PubMed  Google Scholar 

  56. Bechtold DA, Rush SJ, Brown IR. Localisation of the heat-shock protein Hsp70 to the synapse following hyperthermic stress in the brain. J Neurochem 2000; 74:641–646.

    Article  CAS  PubMed  Google Scholar 

  57. Guo ZH, Mattson MP. In Vivo 2-Deoxyglucose Administration Preserves Glucose and Glutamate Transport and Mitochondrial Function in Cortical Synaptic Terminals after Exposure to Amyloid. Exp Neurol 2000; 166:173–179.

    Article  CAS  PubMed  Google Scholar 

  58. Tobaben S, Thakur P, Fernandez-Chacon R et al. A trimeric protein complex functions as a synaptic chaperone machine. Neuron 2001; 31:987–999.

    Article  CAS  PubMed  Google Scholar 

  59. Hay DG, Sathasivam K, Tobaben S et al. Progressive decrease in chaperone protein levels in a mouse model of Huntington’s disease and induction of stress proteins as a therapeutic approach. Hum Mol Genet 2004; 13(13):1389–405.

    Article  CAS  PubMed  Google Scholar 

  60. Gunawardena S, LSG. Polyglutamine diseases and transport problems: Deadly traffic jams on neuronal highways. Arch Neurol 2005; 62(1):46–51.

    Article  PubMed  Google Scholar 

  61. Gauthier LR, Charrin BC, Borrell-Pages M et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004; 118(1):127–138.

    Article  CAS  PubMed  Google Scholar 

  62. Saha AR, Hill J, Utton MA et al. Parkinson’s disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci 2004; 117(7):1017–24.

    Article  CAS  PubMed  Google Scholar 

  63. Terwel D, Dewachter I, Van Leuven F. Axonal transport, tau protein, and neurodegeneration in Alzheimer’s disease. Neuromoleculer Med 2002; 2(2):151–165.

    Article  CAS  Google Scholar 

  64. Willis D, Li KW, Zheng JQ et al. Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci 2005; 25(4):778–791.

    Article  CAS  PubMed  Google Scholar 

  65. Auluck PK, Meulener MC, Bonini NM. Mechanisms of suppression of alpha-synuclein neurotoxicity by Geldanamycin in Drosophila. J Biol Chem 2005; 280(4):2873–8.

    Article  CAS  PubMed  Google Scholar 

  66. Klettner A. The induction of heat shock proteins as a potential strategy to treat neurodegenerative disorders. Drug News Perspect 2004; 17(5):299–306.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Southampton Neuroscience Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK

    Andreas Wyttenbach

  2. Laboratoire Stress Oxydant Chaperons et Apoptose Centre de Génétique Moléculaire et Cellulaire CNRS UMR 5534, Université Claude Bernard Lyon-1, Villeurbanne, France

    André Patrick Arrigo

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  1. Andreas Wyttenbach
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  2. André Patrick Arrigo
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Correspondence to Andreas Wyttenbach .

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Wyttenbach, A., Arrigo, A.P. (2009). The Role of Heat Shock Proteins during Neurodegeneration in Alzheimer’s, Parkinson’s and Huntington’s Disease. In: Heat Shock Proteins in Neural Cells. Neuroscience Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39954-6_7

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