Abstract
The brain is the most complex organ in the human body and the main component of the central nervous system. Because it lacks the ability of regeneration, age is a major risk factor for most common neurodegenerative diseases, which caused an irreversible cognitive impairment. It has been shown that the function of molecular chaperones, majorly heat shock proteins, was compromised and then causes the imbalance of protein homeostasis inside the cell, which is the most influential reason of brain aging. Here, in this review, we discuss the mechanisms underneath the impairment of heat shock protein function during brain aging, including transcriptional regulation, posttranslational modification, and communication across cells and organs.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115. https://doi.org/10.1146/annurev-biochem-060809-095203
Auluck PK, Chan HYE, Trojanowski JQ et al (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 295:865–868. https://doi.org/10.1126/science.1067389
Bali P, Pranpat M, Bradner J et al (2005) Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 280:26729–26734. https://doi.org/10.1074/jbc.C500186200
Bonelli MA, Alfieri RR, Poli M et al (2001) Heat-induced proteasomic degradation of HSF1 in serum-starved human fibroblasts aging in vitro. Exp Cell Res 267:165–172. https://doi.org/10.1006/excr.2001.5237
Boyault C, Zhang Y, Fritah S et al (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 21:2172–2181. https://doi.org/10.1101/gad.436407
Brehme M, Voisine C, Rolland T et al (2014) A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep 9:1135–1150. https://doi.org/10.1016/j.celrep.2014.09.042
Calderwood SK, Murshid A, Prince T (2009) The shock of aging: molecular chaperones and the heat shock response in longevity and aging – a mini-review. Gerontology 55:550–558
Carmichael J, Chatellier J, Woolfson A et al (2000) Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington’s disease. Proc Natl Acad Sci U S A 97:9701–9705. https://doi.org/10.1073/pnas.170280697\n170280697 [pii]
Dou F, Netzer WJ, Takashima A, Xu H (2003a) Heat shock proteins reduce aggregation and facilitate degradation of tau protein
Dou F, Netzer WJ, Tanemura K et al (2003b) Chaperones increase association of tau protein with microtubules. Proc Natl Acad Sci USA 100:721–726
Dou F, Yuan L-D, Zhu J-J (2005) Heat shock protein 90 indirectly regulates ERK activity by affecting Raf protein metabolism. Acta Biochim Biophys Sin Shanghai 37:501–505. https://doi.org/10.1111/j.1745-7270.2005.00069.x
Dou F, Chang X, Ma D (2007) Hsp90 maintains the stability and function of the tau phosphorylating kinase GSK3β. Int J Mol Sci 8:51–60
Du Y, Wang F, Zou J et al (2014) Histone deacetylase 6 regulates cytotoxic α-synuclein accumulation through induction of the heat shock response. Neurobiol Aging 35:2316–2328. https://doi.org/10.1016/j.neurobiolaging.2014.04.029
Fawcett TW, Sylvester SL, Sarge KD et al (1994) Effects of neurohormonal stress and aging on the activation of mammalian heat shock factor 1. J Biol Chem 269:32272–32278
Franco MC, Ye Y, Refakis CA et al (2013) Nitration of Hsp90 induces cell death. Proc Natl Acad Sci 110:E1102–E1111. https://doi.org/10.1073/pnas.1215177110
Franco MC, Ricart KC, Gonzalez AS et al (2015) Nitration of Hsp90 on tyrosine 33 regulates mitochondrial metabolism. J Biol Chem 290:19055–19066. https://doi.org/10.1074/jbc.M115.663278
Gavilán E, Pintado C, Gavilan MP et al (2015) Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress. Neurobiol Aging 36:1953–1963. https://doi.org/10.1016/j.neurobiolaging.2015.02.025
Gezen-Ak D, Dursun E, Hanağası H et al (2013) BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer’s disease or mild cognitive impairment. J Alzheimers Dis 37:185–195. https://doi.org/10.3233/JAD-130497
Goetzl EJ, Boxer A, Schwartz JB et al (2015) Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 85:40–47. https://doi.org/10.1212/WNL.0000000000001702
Graner MW, Cumming RI, Bigner DD (2007) The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences. J Neurosci 27:11214–11227. https://doi.org/10.1523/JNEUROSCI.3588-07.2007
Gutsmann-Conrad A, Heydari AR, You S, Richardson A (1998) The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res 241:404–413. https://doi.org/10.1006/excr.1998.4069
Hightower LE, Guidon PT Jr (1989) Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins. J Cell Physiol 138:257–266
Höhfeld J, Cyr DM, Patterson C (2001) From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep 2:885–890. https://doi.org/10.1093/embo-reports/kve206
Jurivich DA, Qiu L, Welk JF (1997) Attenuated stress responses in young and old human lymphocytes. Mech Ageing Dev 94:233–249
Kaushik S, Cuervo AM (2015) Proteostasis and aging. Nat Med 21:1406–1415. https://doi.org/10.1038/nm.4001
Kovacs JJ, Murphy PJM, Gaillard S et al (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18:601–607. https://doi.org/10.1016/j.molcel.2005.04.021
Kregel KC (2002) Invited review: heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 92:2177–2186. https://doi.org/10.1152/japplphysiol.01267.2001
Lo Cicero A, Stahl PD, Raposo G (2015) Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol 35:69–77. https://doi.org/10.1016/j.ceb.2015.04.013
Locke M, Tanguay RM (1996) Diminished heat shock response in the aged myocardium. Cell Stress Chaperones 1:251–260
López-OtÃn C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Luo W, Dou F, Rodina A et al (2007) Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. Proc Natl Acad Sci USA 104:9511–9516
Mollapour M, Neckers L (2012) Post-translational modifications of Hsp90 and their contributions to chaperone regulation. Biochim Biophys Acta, Mol Cell Res 1823:648–655
Muchowski PJ, Schaffar G, Sittler A et al (2000) Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci 97:7841–7846. https://doi.org/10.1073/pnas.140202897
Murphy PJM, Morishima Y, Kovacs JJ et al (2005) Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. J Biol Chem 280:33792–33799. https://doi.org/10.1074/jbc.M506997200
Nimmanapalli R, Fuino L, Bali P et al (2003) Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res 63:5126–5135
Pernet L, Faure V, Gilquin B et al (2014) HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat shock. Mol Biol Cell 25:4187–4194. https://doi.org/10.1091/mbc.E14-06-1032
Prodromou C (2016) Mechanisms of Hsp90 regulation. Biochem J 473:2439–2452. https://doi.org/10.1042/BCJ20160005
Schneider JL, Villarroya J, Diaz-Carretero A et al (2015) Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging. Aging Cell 14:249–264. https://doi.org/10.1111/acel.12310
Sittler A, Lurz R, Lueder G et al (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 10:1307–1315. https://doi.org/10.1093/hmg/10.12.1307
Slavotinek AM, Biesecker LG (2001) Unfolding the role of chaperones and chaperonins in human disease. Trends Genet 17:528–535
Takeuchi T, Suzuki M, Fujikake N et al (2015) Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. Proc Natl Acad Sci 112:E2497–E2506. https://doi.org/10.1073/pnas.1412651112
Uryu K, Richter-Landsberg C, Welch W et al (2006) Convergence of heat shock protein 90 with ubiquitin in filamentous α-synuclein inclusions of α-synucleinopathies. Am J Pathol 168:947–961. https://doi.org/10.2353/ajpath.2006.050770
Van Oosten-Hawle P, Porter RS, Morimoto RI (2013) Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153:1366–1378. https://doi.org/10.1016/j.cell.2013.05.015
Walsh RC, Koukoulas I, Garnham A et al (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 6:386. https://doi.org/10.1379/1466-1268(2001)006<0386:EISHIH>2.0.CO;2
Walther DM, Kasturi P, Mann M et al (2015) Widespread proteome remodeling and aggregation in aging C. elegans. Cell 161:919–932. https://doi.org/10.1016/j.cell.2015.03.032
Warrick JM, Chan HYE, Gray-Board GL et al (1999) Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet 23:425–428. https://doi.org/10.1038/70532
Yokota T, Mishra M, Akatsu H et al (2006) Brain site-specific gene expression analysis in Alzheimer’s disease patients. Eur J Clin Investig 36:820–830. https://doi.org/10.1111/j.1365-2362.2006.01722.x
Zuehlke AD, Beebe K, Neckers L, Prince T (2015) Regulation and function of the human HSP90AA1 gene. Gene 570:8–16. https://doi.org/10.1016/j.gene.2015.06.018
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (NSFC) (31370768, 31170737, 30970610) and the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Wang, K., Shang, Y., Dou, F. (2018). Brain Aging: Hsp90 and Neurodegenerative Diseases. In: Wang, Z. (eds) Aging and Aging-Related Diseases. Advances in Experimental Medicine and Biology, vol 1086. Springer, Singapore. https://doi.org/10.1007/978-981-13-1117-8_6
Download citation
DOI: https://doi.org/10.1007/978-981-13-1117-8_6
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-1116-1
Online ISBN: 978-981-13-1117-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)