Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling
Open accessAbstract
The ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurodegenerative diseases. We investigated the effects of tau accumulation on proteasome function in a mouse model of tauopathy and in a cross to a UPS reporter mouse (line Ub-G76V-GFP). Accumulation of insoluble tau was associated with a decrease in the peptidase activity of brain 26S proteasomes, higher levels of ubiquitinated proteins and undegraded Ub-G76V-GFP. 26S proteasomes from mice with tauopathy were physically associated with tau and were less active in hydrolyzing ubiquitinated proteins, small peptides and ATP. 26S proteasomes from normal mice incubated with recombinant oligomers or fibrils also showed lower hydrolyzing capacity in the same assays, implicating tau as a proteotoxin. Administration of an agent that activates cAMP-protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasome subunit phosphorylation. In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance.
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After rolipram treatment, increased phosphorylation of PKA and proteasome subunits was seen, indicating enhancement of the proteasome system.
“In addition, increased phosphorylation of PKA — a mediator of proteasome function — and proteasome subunits was seen after rolipram treatment, indicating enhancement of the proteasome system170.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [170]
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Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
Protein degradation and protection against misfolded or damaged proteins.
Goldberg, A. L. (2003) · Nature · doi:10.1038/nature02263 · Cited by 2,088 · see citing works
Self-citationTau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · see citing works
Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome
Finley, D. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.081507.101607 · Cited by 1,764 · see citing works
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · 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
Self-citationResveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., Ke, H., Rehmann, H., Taussig, R., Brown, A. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.017 · Cited by 1,352 · see citing works
The Molecular and Systems Biology of Memory
Kandel, E. R., Dudai, Y., & Mayford, M. R. (2014) · Cell · doi:10.1016/j.cell.2014.03.001 · Cited by 1,134 · see citing works
Trans-Synaptic Spread of Tau Pathology In Vivo
Liu, L., Drouet, V., Wu, J., Witter, M. P., Small, S. A., Clelland, C. L. T., & Duff, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031302 · Cited by 994 · see citing works
Self-citationEnhancement 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
Impaired Proteasome Function in Alzheimer's Disease
Keller, J. N., Hanni, K. B., & Markesbery, W. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750436.x · Cited by 848 · see citing works
Complete subunit architecture of the proteasome regulatory particle
Lander, G. C., Estrin, E., Matyskiela, M. E., Bashore, C., Nogales, E., & Martin, A. (2012) · Nature · doi:10.1038/nature10774 · Cited by 608 · see citing works
Schneider, A., Biernat, J., von Bergen, M., Mandelkow, E., & Mandelkow, E.-M. (1999) · Biochemistry · doi:10.1021/bi981874p · Cited by 564 · see citing works
Wu, J. W., Herman, M., Liu, L., Simoes, S., Acker, C. M., Figueroa, H., Steinberg, J. I., Margittai, M., Kayed, R., Zurzolo, C., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394528 · Cited by 537 · see citing works
Self-citationProteasome inhibition by paired helical filament‐tau in brains of patients with Alzheimer's disease
Keck, S., Nitsch, R., Grune, T., & Ullrich, O. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01642.x · Cited by 483 · see citing works
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
Tai, H., Serrano‐Pozo, A., Hashimoto, T., Frosch, M. P., Spires‐Jones, T. L., & Hyman, B. T. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.033 · Cited by 456 · see citing works
Tau 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
Regulation of the autophagy protein LC3 by phosphorylation
Cherra, S. J., Kulich, S. M., Uechi, G. T., Balasubramani, M., Mountzouris, J. A., Day, B. W., & Chu, C. T. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201002108 · Cited by 341 · see citing works
Proteasomal degradation of tau protein
David, D. C., Layfield, R., Serpell, L., Narain, Y., Goedert, M., & Spillantini, M. G. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01137.x · Cited by 327 · see citing works
Cripps, D., Thomas, S. N., Jeng, Y., Yang, F., Davies, P., & Yang, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512786200 · Cited by 312 · see citing works
Near-atomic resolution structural model of the yeast 26S proteasome
Beck, F., Unverdorben, P., Bohn, S., Schweitzer, A., Pfeifer, G., Sakata, E., Nickell, S., Plitzko, J. M., Villa, E., Baumeister, W. P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213333109 · Cited by 254 · see citing works
A transgenic mouse model of the ubiquitin/proteasome system
Lindsten, K., Menéndez-Benito, V., Masucci, M. G., & Dantuma, N. P. (2003) · Nature Biotechnology · doi:10.1038/nbt851 · Cited by 234 · see citing works
Lokireddy, S., Kukushkin, N. V., & Goldberg, A. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522332112 · Cited by 222 · see citing works
Self-citationDynamics of the Degradation of Ubiquitinated Proteins by Proteasomes and Autophagy
Myeku, N., & Figueiredo-Pereira, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.149252 · Cited by 220 · see citing works
Self-citationPeth, A., Besche, H. C., & Goldberg, A. L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.11.015 · Cited by 211 · see citing works
Self-citationSmith, D. M., Fraga, H., Reis, C. R. S., Kafri, G., & Goldberg, A. (2011) · Cell · doi:10.1016/j.cell.2011.02.005 · Cited by 202 · see citing works
Self-citationZhang, F., Hu, Y., Huang, P. C., Toleman, C. A., Paterson, A. J., & Kudlow, J. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702439200 · Cited by 200 · see citing works
Peth, A., Uchiki, T., & Goldberg, A. L. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.11.002 · Cited by 167 · see citing works
Self-citationThe ATP Costs and Time Required to Degrade Ubiquitinated Proteins by the 26 S Proteasome
Peth, A., Nathan, J. A., & Goldberg, A. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.482570 · Cited by 140 · see citing works
Self-citationProteasomal AAA-ATPases: Structure and function
Bar‐Nun, S., & Glickman, M. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.07.009 · Cited by 131 · see citing works
Deriziotis, P., André, R., Smith, D. M., Goold, R., Kinghorn, K. J., Kristiansen, M., Nathan, J. A., Rosenzweig, R., Krutauz, D., Glickman, M. H., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.224 · Cited by 122 · see citing works
Self-citationUbiquitinated Proteins Activate the Proteasomal ATPases by Binding to Usp14 or Uch37 Homologs*
Peth, A., Kukushkin, N., Bosse, M. L., & Goldberg, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.441907 · Cited by 114 · see citing works
Self-citationSadik, G., Tanaka, T., Kato, K., Yamamori, H., Begum, N. N., Morihara, T., & Takeda, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05716.x · Cited by 114 · see citing works
Saeki, Y., Isono, E., & Toh‐e, A. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)99014-9 · Cited by 107 · see citing works
Verma, R., McDonald, W. H., Yates, J. R., & Deshaies, R. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00308-2 · Cited by 103 · see citing works
Direct cellular delivery of human proteasomes to delay tau aggregation
Han, D. H., Na, H., Choi, W. H., Lee, J. H., Kim, Y. K., Won, C., Lee, S., Kim, K. P., Kuret, J., Min, D., et al. (2014) · Nature Communications · doi:10.1038/ncomms6633 · Cited by 97 · see citing works
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Asai, M., Tsukamoto, O., Minamino, T., et al. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.11.001 · Cited by 96 · see citing works
Lin, J.-T., Chang, W.-C., Chen, H.-M., Lai, H.-L., Chen, C.-Y., Tao, M.-H., & Chern, Y. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01434-12 · Cited by 70 · see citing works
Organotypic Slice Cultures from Transgenic Mice as Disease Model Systems
Duff, K., Noble, W. J., Gaynor, K., & Matsuoka, Y. (2002) · Journal of Molecular Neuroscience · doi:10.1385/jmn:19:3:317 · Cited by 48 · see citing works
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Myeku, N., Wang, H., & Figueiredo‐Pereira, M. E. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.08.051 · Cited by 46 · see citing works
Self-citationZhu, B., Zhang, L., Creighton, J. R., ALEXEYEV, M. F., Strada, S. J., & Stevens, T. (2010) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00431.2009 · Cited by 40 · see citing works
Affinity Purification of Mammalian 26S Proteasomes Using an Ubiquitin-Like Domain
Besche, H. C., & Goldberg, A. L. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-474-2_29 · Cited by 39 · see citing works
Self-citationMetcalfe, M., Huang, Q., & Figueiredo‐Pereira, M. E. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.70 · Cited by 38 · see citing works
Myeku, N., Metcalfe, M., Huang, Q., et al. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-328-8_18 · Cited by 32 · see citing works
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Thomas, S. N., Cripps, D., & Yang, A. J. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-562-6_8 · Cited by 24 · see citing works
Keeping proteasomes under control—a role for phosphorylation in the nucleus
Sha, Z., Peth, A., & Goldberg, A. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115315108 · Cited by 22 · see citing works
Self-citationThe Synthesis and Proteasomal Degradation of a Model Substrate Ub5DHFR
Lam, Y. A., Huang, J., & Showole, O. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)98031-2 · Cited by 9 · see citing works
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- Authors
- Myeku, N., Clelland, C. L., Emrani, S., Kukushkin, N. V., Yu, W. H., Goldberg, A. L., & Duff, K. E.
- Affiliations
- Columbia University (US)
- Harvard University (US)
- New York State Psychiatric Institute (US)
- Corresponding author
- Duff, Karen E
- ORCID
- Venue
- Nature Medicine
- Published
- 2015-12-21
- Volume
- 22
- Issue
- 1
- Pages
- 46-53
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4787271
- OpenAlex
- W2229830115
- Cited by
- 446
- References
- 49
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 43 · 2023: 45 · 2022: 30 · 2021: 49 · 2020: 42 · 2019: 52 · 2018: 48 · 2017: 49 · 2016: 24 · 2015: 2 · 2014: 1
- FWCI
- 30.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM051923, GM051923)
- National Institute of Neurological Disorders and Stroke (R01NS074593, NS074593)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tau accumulation, 26S proteasome, ubiquitin-proteasome system, proteasome dysfunction, tauopathy, cAMP/PKA signaling, ubiquitinated proteins, tau oligomers, tau fibrils, cognitive impairment, neurodegeneration
- MeSH terms
- Cyclic AMP, Animals, Behavior, Animal, Brain, Cognition, Cognition Disorders, Disease Models, Animal, Fluorescent Antibody Technique, Humans, Mice, Transgenic, Immunoblotting, Signal Transduction, tau Proteins, Cyclic AMP-Dependent Protein Kinases, Rolipram, Tauopathies, Proteasome Endopeptidase Complex, Immunoprecipitation, Mice, Ubiquitination, HEK293 Cells, Phosphodiesterase 4 Inhibitors, Native Polyacrylamide Gel Electrophoresis, Protein Aggregation, Pathological, In Vitro Techniques
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