Heat shock proteins (HSPs) or so called stress proteins have multifunctional roles and are involved in many physiological processes, such as cell cycle control, cell proliferation, development, organisation of the cytoarchitecture, regulation of cell death and survival, and play regulatory roles in cellular aging and longevity. They participate in protein synthesis, protein folding, transport and translocalization processes, by acting as molecular chaperones. As a result of a variety of stress situations, HSPs accumulate and help to prevent protein misfolding and aggregation, provide tolerance against further stress situations, and cooperate with the ubiquitin proteasome system during protein quality control. HSPs are differentially expressed in nerve cells and glia, and cell type specific responses to various stressors are observed. Stress proteins may serve as biomarkers to identify stress specificity and localize pathological processes, leading to cell and organelle damage in the nervous system. They can be used as neuropathological markers and are promising targets for therapeutic intervention and drug development.
- Heat Shock
- Heat Shock Protein
- Molecular Chaperone
- Heme Oxygenase
- Ubiquitin Proteasome System
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, access via your institution.
Tax calculation will be finalised at checkout
Purchases are for personal use onlyLearn about institutional subscriptions
Unable to display preview. Download preview PDF.
Jaattela M. Heat shock proteins as cellular lifeguards. Ann Med 1999; 31:261–271.
Helmbrecht K, Zeise E, Rensing L. Chaperones in cell cycle regulation and mitogenic signal transduction: A review. Cell Prolif 2000; 25:585–621.
Rutherford SL, Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature 1998; 396:336–342.
Nollen EAA, Morimoto RI. Chaperoning signaling pathways: Molecular chaperones as stress-sensing heat shock proteins. J Cell Sci 2002; 115:2809–2818.
Liang P, MacRae TH. Molecular chaperones and the cytoskeleton. J Cell Sci 1997; 110:1431–1440.
Head MW, Goldman JE. Small heat shock proteins, the cytoskeleton and inclusion body formation. Neuropath Appl Neurobiol 2000; 26:304–312.
Csermely P. A nonconventional role of molecular chaperones: Involvement in the cytoarchitecture. News Physiol Sci 2001; 15:123–126.
Richter-Landsberg C, Bauer NG. Tau-inclusion body formation in oligodendroglia: The role of stress proteins and proteasome inhibition. Int J Devl Neurosci 2004; 22:443–451.
Söti C, Sreedhart AS, Csermely P. Apoptosis, necrosis and cellular senescence: Chaperone occupancy as a potential switch. Aging cell 2003; 2:39–45.
Sreedhar AS, Csermely P. Heat shock proteins in the regulation of apoptosis: New strategies in tumor therapy. Pharmacol Ther 2004; 101:227–257.
Fink AL. Chaperone-mediated protein folding. Physiol Rev 1999; 79:425–449.
Richter-Landsberg C, Goldbaum O. Stress proteins in neural cells: Functional roles in health and disease. Cell Mol Life Sci 2003; 60:337–349.
Lee AS. The glucose-regulated proteins: Stress induction and clinical applications. Trends Biochem 2001; 26:504–510.
Muchowski PJ, Hays LG, Yates JR et al. ATP and the core α-crystallin domain of the small heat shock protein αB-crystallin. J Biol Chem 1999; 274:20190–20195.
Wang K, Spector A. ATP causes the small heat shock proteins to release denatured protein. Eur J Biochem 2001; 268:6335–6345.
Ciechanover A, Brundin P. The ubiquitin proteasome system in neurodegenerative diseases: Sometimes the chicken, sometimes the egg. Neuron 2003; 40:427–445.
Forman MS, Trojanowski JQ, Lee VMY. Neurodegenerative diseases: A decade of discoveries paves the way for therapeutic breakthroughs. Nature Medicine 2004; 10:1055–1063.
Esser C, Alberti S, Höhfeld J. Cooperation of molecular chaperones with the ubiquitin proteasome system. Biochim Biophys Acta 2004; 1695:171–188.
Lee DH, Goldberg AL. Proteasome inhibitors: Valuable new tools for cell biologists. Trends Cell Biol 1998; 8:397–403.
Kim D, Kim SH, Li GC. Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression. Biochem Biophys Res Comm 1999; 254:264–268.
Goldbaum O, Richter-Landsberg C. Proteolytic stress causes heat shock protein induction, tau-ubiquitination and the recruitment of ubiquitin to tau-positive aggregates in oligodendrocytes in culture. J Neurosci 2004; 24:5748–5757.
Sherman MY, Goldberg AL. Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron 2001; 29:15–32.
Pirkkala L, Nykänen P, Sistonen L. Roles of heat shock transcription factors in regulation of the heat shock response and beyond. FASEB J 2001; 15:1118–1131.
Morimoto RI. Cells in stress: Transcriptional activation of heat shock genes. Science 1993; 259:1409–1410.
Wu C. Heat shock transcription factors: Structure and regulation. Annu Rev Cell Dev Biol 1995; 11:441–469.
Zou J, Guo Y, Guettouche T et al. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 1998; 94:471–480.
Kawazoe Y, Nakai A, Tanabe M et al. Proteasome inhibition leads to the activation of all members of the heat shock factor family. Eur J Biochem 1998; 255:356–362.
Kim D, Li GC. Proteasome inhibitors lactacystin and MG132 inhibit the dephosphorylation of HSF1 after heat shock and suppress thermal induction of heat shock genes. Biochem Biophys Res Comm 1999; 264:352–358.
Pirkkala L, Alastalo TP, Zuo X et al. Disruption of heat shock factor1 reveals an essential role in the ubiquitin proteolytic pathway. Mol Cell Biol 2000; 20:2670–2675.
Dwyer BE, Nishimura RN. Heat shock proteins and neuroprotection in CNS culture. In: Mayer J, Brown I, eds. Heat Shock Proteins in the Nervous System. New York: Academic Press, 1994:101–121.
Sharp FR, Massa SM, Swanson RA. Heat shock protein protection. Trends Neurosci 1999; 22:97–99.
Yenari MA, Giffard RM, Steinberg GK. The neuroprotective potential of heat shock protein 70 (HSP70). Molecular Med Today 1999; 5:525–531.
Goldbaum O, Richter-Landsberg C. Stress proteins in oligodendrocytes: Differential effects of heat shock and oxidative stress. J Neurochem 2001; 78:1233–1242.
Picard D. Heat shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci 2002; 59:1640–1648.
Pratt WB, Toft DO. Regulation of signaling by the hsp90/hsp70-based chaperone machinery. Exp Biol Med 2003; 228:111–133.
Brown IR. Induction of heat shock genes in mammalian brain by hyperthermia and tissue injury. In: Mayer J, Brown I, eds. Heat Shock Proteins in the Nervous System. New York: Academic Press, 1994:31–53.
McClellan AJ, Frydman J. Molecular chaperones and the art of recognizing a lost cause. Nature Cell Biol 2001; 3:E1–E3.
Young JC, Moarefi I, Hartl FU. Hsp90: A specialized but essential protein-folding tool. J Cell Biol 2001; 154:267–273.
Neckers L. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 2002; 8:S55–S61.
Sreedhar AS, Kalmar E, Csermely P et al. Hsp90 isoforms: Functions, expression and clinical importance. FEBS Lett 2004; 562:11–15.
Grammatikakis N, Vultur A, Ramana CV et al. The role of Hsp90N, a new member of the Hsp90 family, in signal transduction and neoplastic transformation. J Biol Chem 2002; 277:8312–8320.
Sreedhar AS, Söti C, Csermely P. Inhibition of Hsp90: A new strategy for inhibiting protein kinases. Biochim Biophys Acta 2004; 1697:233–242.
Sidera K, Samiotaki M, Panayotou G et al. Involvement of cell surface HSP90 in cell migration reveals a novel role in the developing nervous system. J Biol Chem 2004; 279:45379–45388.
Gerges NZ, Tran IC, Backos DS et al. Independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of AMPA receptors. J Neurosci 2004; 24:4758–4766.
Galigniana MD, Harrell JM, Housley PR et al. Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation. Mol Brain Res 2004; 123:27–36.
Whitesell L, Mimnaugh EG, de Costa B et al. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: Essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 1994; 91:8324–8328.
Le Brazidec JY, Kamal A, Busch D et al. Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90. J Med Chem 2004; 47:3865–3873.
Kamal A, Sensintaffar J, Boehm MF et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2002; 425:407–410.
Neckers L, Lee YS. The rules of attraction. Nature 2003; 425:357–359.
Sittler A, Lurz R, Lueder G et al. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Human Mol Genet 2001; 10:1307–1315.
McLean PJ, Klucken J, Shin Y et al. Geldanamycin induced Hsp70 and prevents α-synuclein aggregation and toxicity in vitro. Biochem Biophys Res Comm 2004; 321:665–669.
Lu A, Ran R, Parmentier-Batteur S et al. Geldanamycin induces heat shock proteins in brain and protects against cerebral ischemia. J Neurochem 2002; 81:355–364.
Minami Y, Höhfeld J, Ohtsuka K et al. Regulation of heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40. J Biol Chem 1996; 271:19617–19624.
Michels AA, Kanon B, Konings AWT et al. Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells. J Biol Chem 1997; 272:33283–33289.
Frydman J, Nimmesgern E, Ohtsuka K et al. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 1994; 370:111–117.
Ohtsuka K, Suzuki T. Roles of molecular chaperones in the nervous system. Brain Res Bull 2000; 53:141–146.
Nishimura RN, Dwyer BE, Clegg KB et al. Comparison of the heat shock response in cultured cortical neurons and astrocytes. Mol Brain Res 1991; 9:39–45.
Nishimura RN, Dwyer BE, Vinters HV et al. Heat shock in cultured neurons and astrocytes: Correlation of ultrastructure and heat shock protein synthesis. Neuropathol Appl Neurobiol 1991; 17:139–147.
McCabe T, Simon RP. Hyperthermia induces 72kDa heat shock protein expression in rat brain nonneuronal cells. Neurosci Lett 1993; 159:163–165.
Satoh J, Kim SU. HSP72 induction by heat stress in human neurons and glia cells in culture. Brain Res 1994;653:243–250.
D’Souza DD, Antel JP, Freedman MS. Cytokine induction of heat shock expression in human oligodendrocytes: An interleukin-1-mediated mechanism. J Neuroimmunol 1994;50:17–24.
Satoh J, Yamamura T, Kunishita T et al. Heterogeneous induction of 72-kDa heat shock protein (HSP72) in cultured mouse oligodendrocytes and astrocytes. Brain Res 1992;573:37–43.
Satoh J, Kim SU. Constitutive and inducible expression of heat shock protein HSP72 in oligodendrocytes in culture. Neuroreport 1995;6:1081–1084.
Dwyer BE, Nishimura RN, de Vellis J et al. Regulation of heat shock protein synthesis in rat astrocytes. J Neurosi Res 1991;28:352–358.
Foster JA, Brown IR. Differential induction of heat shock mRNA in oligodendrocytes, microglia and astrocytes following hyperthermia. Mol Brain Res 1997;45:207–218.
Almazan G, Liu HN, Khorchid A et al. Exposure of developing oligodendrocytes to cadmium causes HSP72 induction, free radical generation, reduction in glutathione levels, and cell death. Free Radic Biol Med 2000;29:858–869.
Juurlink BHJ. Type-2 astrocytes have much greater susceptibility to heat stress than type-1 astrocytes. J Neurosi Res 1994;38:196–201.
Beere HM, Green DR. Stress management-heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 2001;11:6–10.
Itoh H, Kobayashi R, Waui H. Mammalian 60 kDa stress protein (chaperonin homolog). Identification, biochemical properties, and localization. J Biol Chem 1995;270:13429–13435.
Brosnan CF, Battistini L, Gao YL et al. Heat shock proteins and multiple sclerosis: A review. J Neuropath Exp Neurol 1996;55:389–402.
Soltys BJ, Gupta RS. Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in mammalian cells. Cell Biol Int 1997;21:315–320.
Maguire M, Coates ARM, Henderson B. Chaperonin 60 unfolds its secrets of cellular communication. Cell Stress Chaperones 2002;7:317–329.
D’Souza SM, Brown IR. Constitutive expression of heat shock proteins Hsp90, Hsc70, Hsp70 and Hsp60 in neural and nonneural tissues of the rat during postnatal development. Cell Stress Chaperones 1998;3:188–199.
Dwyer DS, Liu Y, Miao S et al. Neuronal differentiation in PC12 cells is accompanied by diminished inducibility of Hsp70 and Hsp60 in response to heat and ethanol. Neurochem Res 1996;21:659–666.
Bajramovic JJ, Bsibsi M, Geutskens SB et al. Differential expression of stress proteins in human adult astrocytes in response to cytokines. J Neuroimmunol 2000;106:14–22.
Selmaj K, Brosnan CF, Raine CS. Expression of heat shock protein-65 by oligodendrocytes in vivo and in vitro: Implications for multiple sclerosis. Neurology 1992;42:795–800.
Freedman MS, Buu NN, Ruijs TC et al. Differential expression of heat shock proteins by human glial cells. J Neuroimmunol 1992;41:231–238.
Samali A, Cia JY, Zhivotovsky B et al. Presence of a preapoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. EMBO J 1999;18:2040–2048.
Derham BK, Harding JJ. α-Crystallin as a molecular chaperone. Progr Retinal Eye Res 1999;18:463–509.
Haslbeck M. sHsps and their role in the chaperone network. Cell Mol Life Sci 2002;59:1649–1657.
Jakob U, Buchner J. Assisting spontaneity: The role of Hsp90 and small Hsps as molecular chaperones. Trends Biochem Sci 1994;19:205–211.
Gusev NB, Bogatcheva NV, Marston SB. Structure and properties of small heat shock proteins (sHsp) and their interaction with cytoskeleton proteins. Biochem 2002;67:511–519.
Ciocca DR, Oesterreich S, Chamness GC et al. Biological and clinical implications of heat shock protein 27,000 (HSP27): A review. J Natl Cancer Inst 1993;85:1558–1570.
Ehrnsperger M, Lilie H, Gaestel M et al. The dynamics of Hsp25 quaternary structure. Structure and function of different oligomeric species. J Biol Chem 1999;274:14867–14874.
Horwitz J. Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 1992;89:10449–10453.
DeJong WW, Leunissen JAM, Voorter CEM. Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 1993;10:103–126.
Iwaki T, Iwaki A, Goldman JE. Cellular distribution of alpha B-crystallin in nonlenticular tissues. J Histochem Cytochem 1990;38:31–39.
Kato K, Shinohara H, Kurobe N et al. Tissue distribution and developmental profiles of immunoreactive αB-crystallin in the rat determined with a sensitive immunoassay system. Biochimica Biophysica Acta 1991;1074:201–208.
Lowe J, Mcdermott H, Pike I et al. αB-crystallin expression in nonlenticular tissues and selective presence in ubiquitinated inclusion bodies in human disease. J Pathol 1992;166:61–68.
Muchowski PJ, Bassuk JA, Lubsen NH et al. Human alphaB-crystallin. Small heat shock protein and molecular chaperone. J Biol Chem 1997;272:2578–2582.
Muchowski PJ, Clark JI. ATP-enhanced molecular chaperone functions of the small heat shock protein human αB-crystallin. Proc Natl Acad Sci USA 1998;95:1004–1009.
Biswas A, Das KP. Role of ATP on the interaction of α-crystallin with its substrates and its implications for the molecular chaperone function. J Biol Chem 2004;279:42648–42657.
Dabir D, Trojanowski JQ, Richter-Landsberg C et al. Expression of small heat shock protein αB-crystallin in tauopathies with glial pathology. Am J Pathol 2004;164:143–153.
Schipper HM. Heme oxygenase-1: Role in brain aging and neurodegeneration. Exp Gerontology 2000;35:821–830.
Elbirt KK, Bonkovsky HL. Heme oxygenase: Recent advances in understanding its regulation and role. Proc Assoc Amer Phys 1999;111:438–447.
Sharp FR, Massa SM, Swanson RA. Heat shock protein protection. Trends Neurosci 1999;22:97–99.
Shibahara S, Muller R, Taguchi H et al. Cloning and expression of cDNA for rat heme oxygenase. Proc Natl Acad Sci USA 1985;82:7865–7869.
Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 1986;261:411–419.
McCoubrey Jr WK, Huang TJ, Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 1997;247:725–732.
Dennery PA. Regulation and role of heme oxygenase in oxidative injury. Curr Topics Cellular Regulation 2000;36:181–199.
Ewing JF, Haber SN, Maines MD. Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: Hyperthermia causes rapid induction of mRNA and protein. J Neurochem 1992;58:1140–1149.
Takeda A, Onodera H, Sugimoto A et al. Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia. Brain Res 1994;666:120–124.
Takeda A, Kimpara T, Onodera H et al. Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia. Neurosci Lett 1996;205:169–172.
Koistinaho J, Miettinen S, Keinanen R et al. Long-term induction of haem oxygenase-1 (HSP-32) in astrocytes and microglia following transient focal brain ischaemia in the rat. Eur J Neurosci 1996;8:2265–2272.
Beschorner R, Adjodah D, Schwab JM et al. Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol 2000;100:377–384.
Dwyer BE, Nishimura RN, Lu SY et al. Transient induction of heme oxygenase after cortical stab wound injury. Mol Brain Res 1996;38:251–259.
Dwyer BE, Nishimura RN, Lu SY. Differential expression of heme oxygenase-1 in cultured cortical neurons and astrocytes determined by the aid of a new heme oxygenase antibody. Response to oxidative stress. Mol Brain Res 1995;30:37–47.
Smith KJ, Kapoor R, Felts PA. Demyelination: The role of oxygen and nitrogen species. Brain Pathol 1999;9:69–92.
Schluesener HJ, Seid K. Heme oxygenase-1 in lesions of rat experimental autoimmune encephalomyelitis and neuritis. J Neuroimmunol 2000;110:114–120.
Emerson MR, LeVine SM. Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis: An expanded view of the stress response. J Neurochem 2000;75:2555–2562.
Richter-Landsberg C, Vollgraf U. Mode of cell injury and death after hydrogen peroxide exposure in cultured oligodendroglia cells. Exp Cell Res 1998;244:218–229.
Vollgraf U, Wegner M, Richter-Landsberg C. Activation of AP-1 and NF-kappaB transcription factors is involved in hydrogen peroxide-induced apoptotic cell death of oligodendrocytes. J Neurochem 1999;73:2501–2509.
Mehindate K, Sahlas DJ, Frankel D et al. Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: Implications for multiple sclerosis. J Neurochem 2001;77:1386–1395.
© 2009 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Richter-Landsberg, C. (2009). Heat Shock Proteins. In: Heat Shock Proteins in Neural Cells. Neuroscience Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39954-6_1
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-39952-2
Online ISBN: 978-0-387-39954-6