CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Abstract
Molecular chaperones, ubiquitin ligases and proteasome impairment have been implicated in several neurodegenerative diseases, including Alzheimer's and Parkinson's disease, which are characterized by accumulation of abnormal protein aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau. CHIP also increases tau aggregation. Consistent with this observation, diverse of tau lesions in human postmortem tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show a significant reduction in tau levels. Together these data demonstrate that the Hsp70/CHIP chaperone system plays an important role in the regulation of tau turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Induction of Hsp70 by geldanamycin promotes tau degradation both in vitro and in vivo, whereas deletion of CHIP increases the accumulation of phosphorylated tau and caspase-3 cleaved tau.
“Induction of Hsp70 by geldanamycin promotes tau degradation both in vitro and in vivo, whereas deletion of CHIP increases the accumulation of phosphorylated tau and caspase-3 cleaved tau [167, 171].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [167]
Cites
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., & Crowther, R. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90210-9 · Cited by 2,492 · see citing works
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · see citing works
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444 · see citing works
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374 · see citing works
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · see citing works
Zou, J., Guo, Y., Guettouche, T., Smith, D. F., & Voellmy, R. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81588-3 · Cited by 1,232 · see citing works
Chaperone Suppression of α-Synuclein Toxicity in a <i>Drosophila</i> Model for Parkinson's Disease
Auluck, P. K., Chan, H. Y. E., Trojanowski, J. Q., Lee, V. M.-Y., & Bonini, N. M. (2002) · Science · doi:10.1126/science.1067389 · Cited by 1,227 · see citing works
Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.4051 · Cited by 1,134 · see citing works
Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J., & Crowther, R. A. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03390.x · Cited by 1,037 · see citing works
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins
Connell, P. M., Ballinger, C. A., Jiang, J., Wu, Y., Thompson, L. J., Höhfeld, J., & Patterson, C. (2000) · Nature Cell Biology · doi:10.1038/35050618 · Cited by 1,002 · see citing works
Ballinger, C. A., Connell, P. M., Wu, Y., Hu, Z., Thompson, L. J., Yin, L.-Y., & Patterson, C. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4535 · Cited by 943 · see citing works
Marber, M. S., Mestril, R., H, S., Sayen, M. R., Yellon, D. M., & DILLMANN, W. H. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117815 · Cited by 843 · see citing works
The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation
Meacham, G. C., Patterson, C., Zhang, W., Younger, J. M., & Cyr, D. (2000) · Nature Cell Biology · doi:10.1038/35050509 · Cited by 839 · see citing works
Ebneth, A., Godemann, R., Stamer, K., Illenberger, S., Trinczek, B., Mandelkow, E.-M., & Mandelkow, E. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.3.777 · Cited by 820 · see citing works
Imai, Y., Soda, M., & Takahashi, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000447200 · Cited by 766 · see citing works
Cummings, C. J., Mancini, M. A., Antalffy, B. A., DeFranco, D. B., Orr, H. T., & Zoghbi, H. Y. (1998) · Nature Genetics · doi:10.1038/502 · Cited by 744 · see citing works
Structure and novel exons of the human .tau. gene
Andreadis, A., Brown, W. M., & Kosik, K. S. (1992) · Biochemistry · doi:10.1021/bi00158a027 · Cited by 625 · see citing works
CHIP Is a U-box-dependent E3 Ubiquitin Ligase
Jiang, J., Ballinger, C. A., Wu, Y., Dai, Q., Cyr, D., Höhfeld, J., & Patterson, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101968200 · Cited by 592 · see citing works
Neve, R. L., Harris, P. K. W., Kosik, K. S., Kurnit, D. M., & Donlon, T. A. (1986) · Molecular Brain Research · doi:10.1016/0169-328x(86)90033-1 · Cited by 565 · see citing works
Imai, Y., Soda, M., Hatakeyama, S., Akagi, T., Hashikawa, T., Nakayama, K. I., & Takahashi, R. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00583-x · Cited by 473 · see citing works
CHIP-Hsc70 Complex Ubiquitinates Phosphorylated Tau and Enhances Cell Survival
Shimura, H., Schwartz, D., Gygi, S. P., & Kosik, K. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305838200 · Cited by 469 · see citing works
Chaperones increase association of tau protein with microtubules
Dou, F., Netzer, W. J., Tanemura, K., Li, F., Hartl, F. U., Takashima, A., Gouras, G. K., Greengard, P., & Xu, H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242720499 · Cited by 462 · see citing works
Microtubule organization and dynamics dependent on microtubule-associated proteins
Hirokawa, N. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90119-8 · Cited by 412 · see citing works
Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila
Yang, Y., Nishimura, I., Imai, Y., Takahashi, R., & Lu, B. (2003) · Neuron · doi:10.1016/s0896-6273(03)00143-0 · Cited by 363 · see citing works
CHIP activates HSF1 and confers protection against apoptosis and cellular stress
Dai, Q., Zhang, C., Wu, Y., McDonough, H., Whaley, R. A., Godfrey, V., Li, H., Madamanchi, N. R., Xu, W., Neckers, L., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg529 · Cited by 320 · see citing works
Pharmacological prevention of Parkinson disease in Drosophila
Auluck, P. K., & Bonini, N. M. (2002) · Nature Medicine · doi:10.1038/nm1102-1185 · Cited by 280 · see citing works
Alz-50, Ubiquitin and Tau Immunoreactivity of Neurofibrillary Tangles, Pick Bodies and Lewy Bodies
Love, S., Saitoh, T., Quijada, S., Cole, G. M., & Terry, R. D. (1988) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198807000-00001 · Cited by 242 · see citing works
Fetal‐Type Phosphorylation of the τ in Paired Helical Filaments
Kanemaru, K., Takio, K., Miura, R., Titani, K., & Ihara, Y. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb10039.x · Cited by 197 · see citing works
Yamada, T., McGeer, P. L., & McGeer, E. G. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90145-w · Cited by 192 · see citing works
Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations
Wakabayashi, K., Oyanagi, K., Makifuchi, T., Ikuta, F., Homma, A., Homma, Y., Horikawa, Y., & Tokiguchi, S. (1994) · Acta Neuropathologica · doi:10.1007/bf00293314 · Cited by 157 · see citing works
Molecular chaperones and the art of recognizing a lost cause
McClellan, A. J., & Frydman, J. (2001) · Nature Cell Biology · doi:10.1038/35055162 · Cited by 118 · see citing works
Cardozo, C. P., Michaud, C., Ost, M. C., Fliss, A., Yang, E., Patterson, C., Hall, S. J., & Caplan, A. J. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00680-x · Cited by 106 · see citing works
Hsp70 expression and function during embryogenesis
Luft, J. C., & Dix, D. J. (1999) · Cell Stress and Chaperones · doi:10.1379/1466-1268(1999)004 · Cited by 101 · see citing works
Ubiquitin Lives Up to Its Name
Marx, J. L. (2002) · Science · doi:10.1126/science.297.5588.1792 · Cited by 42 · see citing works
Modulation of tolerance by mutant heat shock transcription factors.
Xia, W., Vilaboa, N. E., Martin, J. W., et al. (1999) · PubMed · doi:10.1006/csac.1998.0113 · Cited by 42 · see citing works
Dai, Q., Wu, Y., Cyr, D., Ballinger, C. A., Patterson, C., Höhfeld, J., & Jiang, J. (2021) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/cmep-zs62 · Cited by 30 · see citing works
Yang, L.-S., & Księżak-Reding, H. (1998) · Acta Neuropathologica · doi:10.1007/s004010050928 · Cited by 23 · see citing works
Cortical tangles in progressive supranuclear palsy
Verny, M., Duyckaerts, C. J., Delaère, P., et al. (1994) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6641-3_14 · Cited by 18 · see citing works
CHIP activates HSF1 and confers protection against apoptosis and cellular stress
Xu, W., Dai, Q., Wu, Y., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/aaye-3j55 · Cited by 14 · see citing works
Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations
Wakabayashi, K., Oyanagi, K., Makifuchi, T., et al. (1994) · Acta Neuropathologica · doi:10.1007/s004010050123 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251 · see citing works
Ubiquitin: structures, functions, mechanisms
Pickart, C. M., & Eddins, M. J. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.09.019 · Cited by 1,406 · see citing works
“CHIP substrates that conform to this paradigm include the cystic fibrosis transmembrane receptor [112], the glucocorticoid receptor [113], and tau [114,115].”
BackgroundTau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · see citing works
Tau in Alzheimer Disease and Related Tauopathies
Iqbal, K., Liu, F., Gong, C., & Grundke, I. (2010) · Current Alzheimer Research · doi:10.2174/156720510793611592 · Cited by 1,122 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
“Induction of Hsp70 by geldanamycin promotes tau degradation both in vitro and in vivo, whereas deletion of CHIP increases the accumulation of phosphorylated tau and caspase-3 cleaved tau [167, 171].”
BackgroundRoles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003 · see citing works
Modulation of neurodegeneration by molecular chaperones
Muchowski, P. J., & Wacker, J. L. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1587 · Cited by 1,021 · see citing works
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W. W., Huang, E. J., Shen, Y., Masliah, E., Mukherjee, C., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.044 · Cited by 949 · see citing works
“The E3 ubiquitin ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) is involved in polyubiquitination and degradation of p-tau (Petrucelli et al., 2004; Shimura et al., 2004).”
Enhancement of proteasome activity by a small-molecule inhibitor of USP14
Lee, B., Lee, M. J., Park, S., Oh, D., Elsasser, S., Chen, P., Gartner, C. A., Dimova, N. V., Hanna, J. W., Gygi, S. P., et al. (2010) · Nature · doi:10.1038/nature09299 · Cited by 943 · see citing works
Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
“Some tau aggregation inhibitors are effective in Neuro2A cell lines overexpressing a 4R tau microtubule repeat domain fragment with a K280 deletion, which promotes its aggregation (Pickhardt et al., 2005).”
BackgroundBiochemistry and Cell Biology of Tau Protein in Neurofibrillary DegenerationPreprint
Mandelkow, E., & Mandelkow, E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006247 · Cited by 839 · see citing works
“It participates in the protein triage process whereby the chaperone system decides whether to keep the protein for refolding or to send it to the proteasome for degradation (Petrucelli et al. 2004; Shimura et al. 2004b).”
BackgroundTau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806 · see citing works
Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities
Hu, C., Yang, J. C., Qi, Z., Wu, H., Wang, B., Zou, F., Mei, H., Liu, J. L., Wang, W., & Liu, Q. (2022) · MedComm · doi:10.1002/mco2.161 · Cited by 811 · see citing works
Rapamycin alleviates toxicity of different aggregate-prone proteins
Berger, Z., Ravikumar, B., Menzies, F. M., Oroz, L. G., Underwood, B. R., Pangalos, M. N., Schmitt, I., Wullner, U., Evert, B. O., O'Kane, C. J., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddi458 · Cited by 657 · see citing works
“We then analysed the effects of rapamycin treatment on the most common tau mutation, P301L, that has been extensively studied both in cells and in mouse transgenics (33,34) and that exhibits strong aggregation properties (35).”
BackgroundMethodDickey, 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) · Journal of Clinical Investigation · doi:10.1172/jci29715 · Cited by 642 · see citing works
“Molecular chaperones are capable of reducing p-tau concentrations and have been shown to prevent tau-associated cellular toxicity (10, 11).”
BackgroundMethodInfluentialSelf-citationMechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628 · see citing works
“Overexpression of Hsp70, which interacts with the heatshock cognate (Hsc) 70-interacting protein (CHIP), a ubiquitin ligase, causes a reduction of tau in transgenic mice [154].”
HECT and RING finger families of E3 ubiquitin ligases at a glance
Metzger, M. B., Hristova, V. A., & Weissman, A. M. (2012) · Journal of Cell Science · doi:10.1242/jcs.091777 · Cited by 622 · see citing works
Liu‐Yesucevitz, L., Bilgutay, A. N., Zhang, Y., Vanderwyde, T., Citro, A., Mehta, T., Zaarur, N., McKee, A. C., Bowser, R. P., Sherman, M. Y., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013250 · Cited by 623 · see citing works
“Reversible aggregation has been noted in other systems, such as the interaction of tau with CHIP [45,46].”
BackgroundSelf-citationTau fragmentation, aggregation and clearance: the dual role of lysosomal processing
Wang, Y., Martinez-Vicente, M., Krüger, U., Kaushik, S., Wong, E., Mandelkow, E.-M., Cuervo, A. M., & Mandelkow, E. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp367 · Cited by 617 · see citing works
“In AD brain, hsc70 is associated with neurofibrillary tangles (36) and has been described to interact with Tau (19).”
BackgroundInfluentialPromoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing
Boland, B., Yu, W. H., Corti, O., Mollereau, B., Henriques, A., Bézard, E., Pastores, G., Rubinsztein, D. C., Nixon, R. A., Duchen, M. R., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.109 · Cited by 552 · see citing works
Phosphorylated Tau in Alzheimer’s Disease and Other Tauopathies
Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112841 · Cited by 509 · see citing works
“CHIP, a ubiquitin ligase, enhances the ubiquitination of the tau and also increases tau aggregation [72].”
BackgroundSmall heat shock proteins: molecular structure and chaperone function
Sun, Y., & MacRae, T. H. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5190-4 · Cited by 502 · see citing works
Regulation of proteasome activity in health and disease
Schmidt, M., & Finley, D. J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.08.012 · Cited by 461 · see citing works
Heat Shock Protein 70 (Hsp70) as an Emerging Drug Target
Evans, C. G., Chang, L., & Gestwicki, J. E. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100054f · Cited by 438 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Zhang, M., Windheim, M., Roe, S. M., Peggie, M. W., Cohen, P., Prodromou, C., & Pearl, L. H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.09.023 · Cited by 420 · see citing works
“, 2004), microtubule-associated Tau protein (Hatakeyama et al., 2004; Petrucelli et al., 2004; Shimura et al., 2004), cystic-fibrosis transmembrane-conductance regulator (Meacham et al.”
BackgroundTau Protein Modifications and Interactions: Their Role in Function and Dysfunction
Mietelska‐Porowska, A., Wasik, U., Goras, M., Filipek, A., & Niewiadomska, G. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15034671 · Cited by 407 · see citing works
“Dickey et al. [194] showed that protein kinase Akt and ubiquitin ligase CHIP co-regulate tau degradation through coordinated interactions involving Hsp90.”
BackgroundInfluentialPosttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains
Arakhamia, T., Lee, C. E., Carlomagno, Y., Kumar, M., Duong, D. M., Wesseling, H., Kundinger, S. R., Wang, K., Williams, D., Deture, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.027 · Cited by 400 · see citing works
Self-citationMicrotubule-associated protein tau in development, degeneration and protection of neurons
Wang, J., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 395 · see citing works
17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration
Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., & Sobue, G. (2005) · Nature Medicine · doi:10.1038/nm1298 · Cited by 395 · see citing works
Aβ inhibits the proteasome and enhances amyloid and tau accumulation
Tseng, B. P., Green, K. N., Chan, J. L., Blurton-Jones, M., & LaFerla, F. M. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.014 · Cited by 384 · see citing works
“More recently, it has been demonstrated that CHIP (carboxyl terminus of the Hsc70-interacting protein), a protein thought to be involved the process of quality-control of proteins as well as being an E3-ligase, regulates the degradation of tau and may prevent its aggregation (Murata et al., 2003, 2001; Petrucelli et a…”
BackgroundResultHistone deacetylase 6 interacts with the microtubule‐associated protein tau
Ding, H., Dolan, P. J., & Johnson, G. V. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05564.x · Cited by 387 · see citing works
“Existence of chaperones, ubiquitin ligases, and proteasome components in tau pathology clearly indicates that various cellular machineries might be actively utilized to cope with abnormal tau accumulation (Dou et al. 2003; Petrucelli et al. 2004; Fergusson et al. 1996).”
BackgroundThe Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases
Lackie, R. E., Maciejewski, A., Ostapchenko, V. G., Marques-Lopes, J., Choy, W., Duennwald, M. L., Prado, V. F., & Prado, M. A. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00254 · Cited by 375 · see citing works
“A number of studies have shown that these hyperphosphorylated tau species can be recognized by Hsps and their co-chaperones, including Hsp27, Hsp70, CHIP, and αB crystalline, in order to repair malignant tau or proceed with its recycling (Dou et al., 2003; Dabir et al., 2004; Petrucelli et al., 2004; Shimura et al., 2…”
BackgroundInfluentialTau degradation: The ubiquitin–proteasome system versus the autophagy-lysosome system
Lee, M. J., Lee, J. H., & Rubinsztein, D. C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.001 · Cited by 364 · see citing works
Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
“In contrast, other groups have reported that both mono- and polyubiquitination contribute to the formation of insoluble protein inclusions present in neurodegenerative diseases (96, 117) and that the induction of tau ubiquitination in cell cultures increases aggregation (102).”
BackgroundAn acetylation switch controls TDP-43 function and aggregation propensity
Cohen, T. J., Hwang, A. W., Restrepo, C. R., Yuan, C., Trojanowski, J. Q., & Lee, V. M. ‐. (2015) · Nature Communications · doi:10.1038/ncomms6845 · Cited by 357 · see citing works
Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42
LIU, R., Barkhordarian, H., Emadi, S., PARK, C., & Sierks, M. R. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.003 · Cited by 340 · see citing works
“, 1999); (3) proteins, such as chaperones and proteasomal proteins (Petrucelli et al., 2004; Xie and Guo, 2004); (4) enzymes, such as angiotensinconverting enzyme (ACE) (Hu et al.”
BackgroundInfluentialAccelerated neurodegeneration through chaperone-mediated oligomerization of tau
Blair, L. J., Nordhues, B. A., Hill, S. E., Scaglione, K. M., O’Leary, J. C., Fontaine, S. N., Breydo, L., Zhang, B., Li, P., Wang, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69003 · Cited by 322 · see citing works
“an Hsp90 cochaperone that can facilitate tau clearance through the proteasome (52, 53), increasing FKBP51 levels were able to displace CHIP from Hsp90 and preserve tau levels (Figure 6E).”
Shin, Y., Klucken, J., Patterson, C., Hyman, B. T., & McLean, P. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503326200 · Cited by 328 · see citing works
GSK3: a possible link between beta amyloid peptide and tau protein
Hernández, F., Gómez de Barreda, E., Fuster-Matanzo, A., Lucas, J. J., & Avila, J. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2009.09.011 · Cited by 327 · see citing works
Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52
Jo, C., Gundemir, S., Pritchard, S., Jin, Y. N., Rahman, I., & Johnson, G. V. W. (2014) · Nature Communications · doi:10.1038/ncomms4496 · Cited by 323 · see citing works
“A complex consisting of the E3 ligase CHIP (C terminus of Hsp70-interacting protein) in conjunction with several chaperones likely plays a role in maintaining tau in a functional conformation or directing it towards the degradation machinery 8, 44–46 .”
The Mechanistic Links Between Proteasome Activity, Aging and Agerelated Diseases
Sáez, I., & Vı́lchez, D. (2014) · Current Genomics · doi:10.2174/138920291501140306113344 · Cited by 318 · see citing works
“The ubiquitin ligase CHIP promotes tau degradation [122, 123].”
BackgroundInfluentialBianco, C. L., Schneider, B. L., Bauer, M., Sajadi, A., Brice, A., Iwatsubo, T., & Aebischer, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405313101 · Cited by 322 · see citing works
Jana, N. R., Dikshit, P., Goswami, A., Kotliarova, S. E., Murata, S., Tanaka, K., & Nukina, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412042200 · Cited by 323 · see citing works
Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation
Babu, J. R., Geetha, T., & Wooten, M. W. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03181.x · Cited by 315 · see citing works
“Recently, two groups have reported that tau is K63 polyubiquitinated by the E3-CHIP (Petrucelli et al. 2004; Shimura et al. 2004).”
BackgroundSmall Ubiquitin-like Modifier (SUMO) Modification of Natively Unfolded Proteins Tau and α-Synuclein
Dorval, V., & Fraser, P. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510127200 · Cited by 319 · see citing works
Liang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., et al. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00242.2007 · Cited by 309 · see citing works
Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases
Zheng, Q., Huang, T. Y., Zhang, L., Zhou, Y., Luo, H., Xu, H., & Wang, X. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00303 · Cited by 312 · see citing works
“CHIP and its binding protein Hsp70 can induce the ubiquitination and degradation of phosphorylated tau (Petrucelli et al., 2004; Shimura et al., 2004), deletion of CHIP leads to the accumulation of nonaggregated, hyperphosphorylated, as well as caspase-3-cleaved tau (Dickey et al., 2006).”
BackgroundCook, C. N., Carlomagno, Y., Gendron, T. F., Dunmore, J. H., Scheffel, K., Stetler, C. T., Davis, M., Dickson, D. W., Jarpe, M. B., Deture, M. A., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt402 · Cited by 309 · see citing works
“E1 (1:1000; human-specific tau antibody) was generated by our group against amino acid residues 19–33 within exon 1 of human tau (7,20,44).”
MethodSelf-citationHeat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases
Neef, D. W., Jaeger, A. M., & Thiele, D. J. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3453 · Cited by 307 · see citing works
Alpha-synuclein and tau: teammates in neurodegeneration?
Moussaud, S., Jones, D. R., Moussaud-Lamodière, E. L., Delenclos, M., Ross, O. A., & McLean, P. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-43 · Cited by 291 · see citing works
“Heat shock proteins (HSPs) increase the association of tau with microtubules and regulate tau degradation, ubiquitination and phosphorylation [164,165].”
BackgroundRodríguez-Navarro, J. A., Rodríguez, L., Casarejos, M. J., Solano, R. M., Gómez, A., Perucho, J., Cuervo, A. M., García de Yébenes, J., & Mena, M. A. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.014 · Cited by 298 · see citing works
“Parkin and tau interaction has been described after overexpression of both proteins (Petrucelli et al., 2004).”
Autophagic degradation of tau in primary neurons and its enhancement by trehalose
Krüger, U., Wang, Y., Kumar, S., & Mandelkow, E.-M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.009 · Cited by 297 · see citing works
“A number of reports have demonstrated that, in principle, tau can be degraded by the proteasome (David et al., 2002; Dickey et al., 2007; Petrucelli et al., 2004; Zhang et al., 2005).”
BackgroundImmunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model
Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-10.2010 · Cited by 272 · see citing works
“Normal tau and at least certain species of nonaggregated hyperphosphorylated tau are likely degraded by the proteosome system as other soluble proteins (Petrucelli et al., 2004), whereas upon aggregation under pathological conditions, clearance through the autophagy/lysosomal system should be favored.”
BackgroundDisease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria
Cummins, N., Tweedie, A., Zuryn, S., Bertran‐Gonzalez, J., & Götz, J. (2019) · The EMBO Journal · doi:10.15252/embj.201899360 · Cited by 267 · see citing works
“In support of our data, Parkin and tau have also been demonstrated to co-immunoprecipitate in other cell types (Petrucelli et al , 2004; Moore et al , 2008).”
The ubiquitin‐proteasome system in Alzheimer's disease
Oddo, S. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00276.x · Cited by 262 · see citing works
“368 protein (CHIP), an E3 ubiquitin ligase that ubiquitinates tau for degradation by the proteasome [99, 100].”
BackgroundThe ubiquitin–proteasome pathway in Parkinson's disease and other neurodegenerative diseases
Ross, C. A., & Pickart, C. M. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.10.006 · Cited by 257 · see citing works
The Chaperone-associated Ubiquitin Ligase CHIP Is Able to Target p53 for Proteasomal Degradation
Esser, C., Scheffner, M., & Höhfeld, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501574200 · Cited by 260 · see citing works
Mocanu, M.-M., Nissen, A., Eckermann, K., Khlistunova, I., Biernat, J., Drexler, D., Petrova, O., Schönig, K., Bujard, H., Mandelkow, E., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2824-07.2008 · Cited by 297 · see citing works
“Our proaggregation mice displayed complete reversibility of the changes involving TauRD/ K280 [i.e., once the expression ceased, the protein disappeared in soluble and aggregated form within 6 weeks, consistent with proteasomal degradation (Petrucelli et al., 2004)].”
BackgroundMin, J.-N., Whaley, R. A., Sharpless, N. E., Lockyer, P., Portbury, A. L., & Patterson, C. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00296-08 · Cited by 256 · see citing works
“CHIP recognizes, ubiquitinates, and degrades unfolded chaperone substrates (9, 30, 34).”
BackgroundDickey, C. A., Yue, M., Lin, W.-L., Dickson, D. W., Dunmore, J. H., Lee, W. C., Zehr, C., West, G., Cao, S., Clark, A. M. K., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0746-06.2006 · Cited by 248 · see citing works
“The antibodies used were as follows: rabbit polyclonal CHIP antibody (1:1000) (Petrucelli et al., 2004); rabbit polyclonal total tau and ubiquitin antibodies (1:1000; Dako, Carpinteria, CA); Tau5 and Tau-C3 [mouse monoclonal total tau antibody (1:1000) and a monoclonal antibody recognizing tau…”
BackgroundMethodResultInfluentialSelf-citationHsp70 – a master regulator in protein degradation
Fernández-Fernández, M. R., Gragera, M., Ochoa‐Ibarrola, L., Quintana‐Gallardo, L., & Valpuesta, J. (2017) · FEBS Letters · doi:10.1002/1873-3468.12751 · Cited by 250 · see citing works
Tau Proteins and Tauopathies in Alzheimer’s Disease
Chong, F. P., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0574-1 · Cited by 248 · see citing works
Tau in neurodegenerative disease
Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.23 · Cited by 222 · see citing works
“The carboxy-terminus of heat shock protein 70-interacting protein (CHIP), which is identified as the ubiquitin ligase, bonds with the phosphorylated tau, cooperates with ubiquitin and subsequently target tau to the proteasome (106).”
BackgroundPratt, W. B., Gestwicki, J. E., Osawa, Y., & Lieberman, A. P. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124332 · Cited by 237 · see citing works
Cellular and pathological functions of tau
Bravo, C. P., Naguib, S. A., & Gan, L. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00753-9 · Cited by 245 · see citing works
“Using various ubiquitin linkages and at distinct tau residues, three E3 ubiquitin ligases ubiq-uitylate tau: the C terminus of the Hsp70-interacting protein, TNF receptor-associated factor 6 and membrane-associated RING-CH7 74–78 , indicating diverse degradation mechanisms.”
Root, J. T., Merino, P., Nuckols, A., Johnson, M. A., & Kukar, T. L. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105360 · Cited by 230 · see citing works
Luo, H.-B., Xia, Y.-Y., Shu, X.-J., Liu, Z.-C., Feng, Y., Liu, X.-H., Yu, G., Yin, G., Xiong, Y.-S., Zeng, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417548111 · Cited by 236 · see citing works
“When the cells are exposed to the stresses, CHIP, a ubiquitin ligase that interacts directly with Hsp70/90, can induce tau ubiquitination and thus selectively reduce the level of detergent insoluble tau (17).”
BackgroundCHIP Suppresses Polyglutamine Aggregation and ToxicityIn VitroandIn Vivo
Miller, V. M., Nelson, R. F., Gouvion, C. M., Williams, A. J., Rodríguez-Lebrón, E., Harper, S. Q., Davidson, B. L., Rebagliati, M. R., & Paulson, H. L. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3001-05.2005 · Cited by 236 · see citing works
Dedmon, M. M., Christodoulou, J. C., Wilson, M. R., & Dobson, C. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413024200 · Cited by 235 · see citing works
Chemical Manipulation of Hsp70 ATPase Activity Regulates Tau Stability
Jinwal, U. K., Miyata, Y., Koren, J., Jones, J. R., Trotter, J. H., Chang, L., O’Leary, J. C., Morgan, D., Lee, D. C., Shults, C. L., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3345-09.2009 · Cited by 231 · see citing works
“Genetic evidence has previously suggested that increasing Hsp70 levels leads to increased binding to tau, which was necessary for CHIP-mediated ubiquitination and degradation (Petrucelli et al., 2004).”
BackgroundInfluentialAkt and CHIP coregulate tau degradation through coordinated interactions
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) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709180105 · Cited by 226 · see citing works
Self-citationTau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
Chesser, A. S., Pritchard, S. M., & Johnson, G. V. W. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00122 · Cited by 219 · see citing works
“However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100).”
BackgroundTau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
“show that CHIP overexpression can promote tau aggregation [285], and ubiquitination of tau by axotrophin significantly reduces the affinity of tau protein to microtubules [292].”
BackgroundUbiquitin–proteasome system and Parkinson's disease
Olanow, C. W., & McNaught, K. S. P. (2006) · Movement Disorders · doi:10.1002/mds.21013 · Cited by 213 · see citing works
Ma, Q., Zuo, X., Yang, F., Ubeda, O. J., Gant, D. J., Alaverdyan, M., Teng, E., Hu, S., Chen, P., Maiti, P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.393751 · Cited by 212 · see citing works
“Overexpression of inducible HSP70 reduces soluble and insoluble Tau levels in aged mice (57).”
BackgroundIn vivo evidence of CHIP up‐regulation attenuating tau aggregation
Sahara, N., Murayama, M., Mizoroki, T., Urushitani, M., Imai, Y., Takahashi, R., Murata, S., Tanaka, K., & Takashima, A. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03272.x · Cited by 208 · see citing works
“Immunohistochemical studies found CHIP co-localized with tau-positive lesions in neurons and glia (Petrucelli et al. 2004).”
BackgroundInfluentialBeyer, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0104-6 · Cited by 208 · see citing works
“The functional signiWcance of -synuclein SUMO1 conjugation remains unknown, but the fact that -synuclein can be degraded by the proteasome through both ubiquitin dependent [6, 101, 114] and independent processes [124] suggests that a similar SUMOdependent competition is operative in both pathways.”
BackgroundAutophagy in Alzheimer’s disease
Zare-shahabadi, A., Masliah, E., Johnson, G. V. W., & Rezaei, N. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0076 · Cited by 204 · see citing works
“There are reports that have demonstrated UPS as a principal τ degradation system (David et al., 2002; Petrucelli et al., 2004; Zhang et al., 2005; Dickey et al., 2007).”
Wang, Y. P., Biernat, J., Pickhardt, M., Mandelkow�, E., & Mandelkow�, E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703676104 · Cited by 205 · see citing works
Updates in Alzheimer's disease: from basic research to diagnosis and therapies
Liu, E., Zhang, Y., & Wang, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00432-x · Cited by 220 · see citing works
“On the other hand, Hsp70 and Hsp104 show inhibitory effects on tau seeding and aggregation [451, 452].”
BackgroundMechanisms of Suppression of α-Synuclein Neurotoxicity by Geldanamycin in Drosophila
Auluck, P. K., Meulener, M. C., & Bonini, N. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412106200 · Cited by 201 · see citing works
Al‐Ramahi, I., Lam, Y. C., Chen, H.-K., Gouyon, B., Zhang, M., Perez, A. M., Branco, J., de Haro, M., Patterson, C., Zoghbi, H. Y., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601603200 · Cited by 198 · see citing works
Tapia‐Rojas, C., Cabezas-Opazo, F., Deaton, C. A., Vergara, E. H., Johnson, G. V. W., & Quintanilla, R. A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.005 · Cited by 195 · see citing works
“In vitro, overexpression studies showed that the E3 ubiquitin ligase CHIP (C-terminus of HSC70-interacting protein) interacts with Hsp70/90 and promotes ubiquitylation of tau (Petrucelli et al., 2004).”
BackgroundAllosteric Drugs: The Interaction of Antitumor Compound MKT-077 with Human Hsp70 Chaperones
Rousaki, A., Miyata, Y., Jinwal, U. K., Dickey, C. A., Gestwicki, J. E., & Zuiderweg, E. R. P. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.06.003 · Cited by 195 · see citing works
The Ubiquitin-Proteasome System and the Autophagic-Lysosomal System in Alzheimer Disease
Ihara, Y., Morishima-Kawashima, M., & Nixon, R. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006361 · Cited by 190 · see citing works
“…it has been reported that the E3 ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) binds to tau and is involved in the degradation of abnormal forms of tau, including insoluble tau and hyperphosphorylated tau, coordinately with Hsp70 (Petrucelli et al. 2004; Dickey et al. 2006).”
BackgroundCHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3
Seo, J., Lee, E.-W., Sung, H., Seong, D., Dondelinger, Y., Shin, J., Jeong, M., Lee, H.-K., Kim, J.-H., Han, S. Y., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3314 · Cited by 182 · see citing works
Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation
Wang, A. M., Miyata, Y., Klinedinst, S., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1140 · Cited by 186 · see citing works
Membrane Trafficking Pathways in Alzheimer 's Disease
Rajendran, L., & Annaert, W. G. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01332.x · Cited by 186 · see citing works
“Phosphorylated tau is polyubiquitinated implying proteasomal breakdown as an important clearing mechanism (147, 148).”
BackgroundSTUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy
Ferreira, J. V., Fofo, H., Bejarano, E., Bento, C. F., Ramalho, J. S., Girão, H., & Pereira, P. (2013) · Autophagy · doi:10.4161/auto.25190 · Cited by 181 · see citing works
Putcha, P., Danzer, K. M., Kranich, L. R., Scott, A., Silinski, M. A. R., Mabbett, S. R., Hicks, C. D., Veal, J. M., Steed, P. M., Hyman, B. T., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.158436 · Cited by 179 · see citing works
“Furthermore, Hsp90-CHIP complexes can target and selectively degrade phosphorylated tau-protein implicated in Alzheimer’s disease (Petrucelli et al., 2004), and Hsp90 inhibitors are also neuroprotective against toxicity caused by A aggregation (Ansar et al., 2007) as well as existing and induced…”
BackgroundThe Cochaperone BAG2 Sweeps Paired Helical Filament- Insoluble Tau from the Microtubule
Carrettiero, D. C., Hernández, I., Neveu, P. A., Papagiannakopoulos, T. Y., & Kosik, K. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4660-08.2009 · Cited by 175 · see citing works
“The Tau protein triage system uses a complex consisting of the E3 ligase CHIP (C terminus of Hsp70-interacting protein) in conjunction with several chaperones to refold Tau or direct it toward the degradation machinery (Petrucelli et al., 2004; Shimura et al., 2004).”
BackgroundMechanisms tailoring the expression of heat shock proteins to proteostasis challenges
Boopathy, L. R. A., Jacob‐Tomas, S., Alecki, C., & Vera, M. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101796 · Cited by 178 · see citing works
Geldanamycin induces Hsp70 and prevents α-synuclein aggregation and toxicity in vitro
McLean, P. J., Klucken, J., Shin, Y., & Hyman, B. T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.021 · Cited by 177 · see citing works
CHIP Targets Toxic α-Synuclein Oligomers for Degradation
Tetzlaff, J. E., Putcha, P., Outeiro, T. F., Ivanov, A., Berezovska, O., Hyman, B. T., & McLean, P. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802283200 · Cited by 175 · see citing works
Poppek, D., Keck, S., Ermak, G., Jung, T., Stolzing, A., Ullrich, O., Davies, K. J. A., & Grune, T. (2006) · Biochemical Journal · doi:10.1042/bj20060463 · Cited by 174 · see citing works
Lee, G. S., & Leugers, C. J. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00004-7 · Cited by 166 · see citing works
Degradation of tau protein by autophagy and proteasomal pathways
Wang, Y., & Mandelkow, E. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120071 · Cited by 166 · see citing works
Statins reduce neuronal α‐synuclein aggregation in in vitro models of Parkinson’s disease
Bar‐On, P., Crews, L. A., Koob, A. O., Mizuno, H., Adame, A., Spencer, B. J., & Masliah, E. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05254.x · Cited by 166 · see citing works
“2005), immunoblot analysis was performed with neuronal cells fractionated into detergent soluble and insoluble fractions, as previously described with minor modifications (Petrucelli et al. 2004; Ho et al. 2005).”
Method
- Authors
- Petrucelli, L.
- Affiliations
- Mayo Clinic in Florida (US)
- Corresponding author
- Petrucelli, L.
- ORCID
- Petrucelli, L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-28
- Volume
- 13
- Issue
- 7
- Pages
- 703-714
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2168079270
- Cited by
- 735
- References
- 41
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 32 · 2023: 35 · 2022: 39 · 2021: 37 · 2020: 35 · 2019: 25 · 2018: 33 · 2017: 30 · 2016: 30 · 2015: 38 · 2014: 34 · 2013: 28 · 2012: 32
- FWCI
- 19.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- CHIP, HSP70, tau protein, ubiquitination, protein degradation, tau aggregation, molecular chaperones, ubiquitin ligase
- MeSH terms
- Heat Shock Transcription Factors, Animals, Cell Line, Detergents, DNA-Binding Proteins, Genetic Vectors, Humans, Immunohistochemistry, Lac Operon
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
