The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration

Deger, Jennifer M.; Gerson, Julia E.; Kayed, Rakez

doi:10.1111/acel.12359

Cited by 69Alzheimer's disease research and treatmentsUbiquitin and proteasome pathwaysParkinson's Disease Mechanisms and Treatments

The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration

Open access

Deger, Jennifer M., Gerson, Julia E., Kayed, Rakez·2015·Aging Cell

DOI 10.1111/acel.12359PMC PMC4568959

Open this paper in CoChat — free account Open PDF

Abstract

Various neurodegenerative diseases are characterized by the accumulation of amyloidogenic proteins such as tau, α-synuclein, and amyloid-β. Prior to the formation of these stable aggregates, intermediate species of the respective proteins-oligomers-appear. Recently acquired data have shown that oligomers may be the most toxic and pathologically significant to neurodegenerative diseases such as Alzheimer's and Parkinson's. The covalent modification of these oligomers may be critically important for biological processes in disease. Ubiquitin and small ubiquitin-like modifiers are the commonly used tags for degradation. While the modification of large amyloid aggregates by ubiquitination is well established, very little is known about the role ubiquitin may play in oligomer processing and the importance of the more recently discovered sumoylation. Many proteins involved in neurodegeneration have been found to be sumoylated, notably tau protein in brains afflicted with Alzheimer's. This evidence suggests that while the cell may not have difficulty recognizing dangerous proteins, in brains afflicted with neurodegenerative disease, the proteasome may be unable to properly digest the tagged proteins. This would allow toxic aggregates to develop, leading to even more proteasome impairment in a snowball effect that could explain the exponential progression in most neurodegenerative diseases. A better understanding of the covalent modifications of oligomers could have a huge impact on the development of therapeutics for neurodegenerative diseases. This review will focus on the proteolysis of tau and other amyloidogenic proteins induced by covalent modification, and recent findings suggesting a relationship between tau oligomers and sumoylation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1111/acel.12359

Cites

111 of 111 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Tau inhibits proteasome activity.
“Interestingly, as with autophagic degradation, tau inhibits proteasome activity87”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [87]
Tau pathology can become self-perpetuating once aggregates are present in neurons.
“suggesting that tau pathology can become self-perpetuating once aggregates are present in neurons.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [87]
Differences in proteostasis affecting UPS function will impact the clinical translational potential of any degrader targeting tau to the proteasome.
“This aspect will impact the clinical translational potential of any degrader targeting tau to the proteasome”
From Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models (2019) · cites this paper as Deger et al., 2015

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Protein aggregation and neurodegenerative disease
Ross, C. A., & Poirier, M. A. (2004) · Nature Medicine · doi:10.1038/nm1066 · Cited by 3,454 · see citing works
α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 3,151 · see citing works
Neurodegenerative Tauopathies
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,192 · see citing works
A Drosophila model of Parkinson's disease
Feany, M., & Bender, W. (2000) · Nature · doi:10.1038/35006074 · Cited by 2,145 · 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
Comparative Genomics of the Eukaryotes
Rubin, G. M., Yandell, M. D., Wortman, J. R., Gabor, G. L., Miklos, Nelson, C. R., Hariharan, I. K., Fortini, M. E., Li, P. W., Apweiler, R., et al. (2000) · Science · doi:10.1126/science.287.5461.2204 · Cited by 1,698 · cited 1× · see citing works
“Although the data from this model have provided no evidence that a synuclein homolog exists (Rubin et al., 2000), these flies express human asynuclein more readily than transgenic mice, suggesting that vertebrates or possibly mammals have developed mechanisms that prevent asynuclein assembly.”
Background
UBIQUITIN-DEPENDENT PROTEIN DEGRADATION
Hochstrasser, M. (1996) · Annual Review of Genetics · doi:10.1146/annurev.genet.30.1.405 · Cited by 1,695 · see citing works
Protein Modification by SUMO
Johnson, E. S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.074118 · Cited by 1,675 · see citing works
SUMO
Hay, R. T. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.012 · Cited by 1,623 · see citing works
The ubiquitin pathway in Parkinson's disease
Leroy, E., Boyer, R., Auburger, G. W. J., Leube, B., Ulm, G., Mezey, É., Harta, G., Brownstein, M., Jonnalagada, S., Chernova, T., et al. (1998) · Nature · doi:10.1038/26652 · Cited by 1,572 · see citing works
Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques
Katzman, R., Terry, R., DeTeresa, R., Brown, T., Davies, P., Fuld, P., Renbing, X., & Peck, A. (1988) · Annals of Neurology · doi:10.1002/ana.410230206 · Cited by 1,225 · see citing works
Parkinson's disease. Second of two parts.
Lang, A., & Lozano, A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810153391607 · Cited by 1,193 · see citing works
Identification of two distinct synucleins from human brain
Jakes, R., Spillantini, M. G., & Goedert, M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00395-5 · Cited by 1,080 · see citing works
Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson's disease
Shimura, H., Schlossmacher, M. G., Hattori, N., Frosch, M. P., Trockenbacher, A., Schneider, R., Mizuno, Y., Kosik, K. S., & Selkoe, D. J. (2001) · Science · doi:10.1126/science.1060627 · Cited by 1,053 · see citing works
Function and structure of inherently disordered proteins
Dunker, A. K., Silman, I., Uversky, V. N., & Sussman, J. L. (2008) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.10.002 · Cited by 963 · see citing works
Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding
Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q., & Lee, V. M. Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90057-x · Cited by 903 · see citing works
Functional Heterogeneity of Small Ubiquitin-related Protein Modifiers SUMO-1 versus SUMO-2/3
Saitoh, H., & Hinchey, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.9.6252 · Cited by 897 · see citing works
Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding
Biernat, J., Gustke, N., Drewes, G., Mandelkow, E., & Mandelkow, E. (1993) · Neuron · doi:10.1016/0896-6273(93)90279-z · Cited by 796 · see citing works
Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease.
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80536-5 · Cited by 779 · see citing works
SUMO—Nonclassical Ubiquitin
Melchior, F. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.591 · Cited by 773 · see citing works
SUMO and ubiquitin in the nucleus: different functions, similar mechanisms?Preprint
Gill, G. (2004) · Genes & Development · doi:10.1101/gad.1214604 · Cited by 752 · see citing works
Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation
Serpell, L. C., Berriman, J. A., Jakes, R., Goedert, M., & Crowther, R. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4897 · Cited by 748 · see citing works
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms
Andorfer, C., Kress, Y., Espinoza, M., De Silva, R., Tucker, K. L., Barde, Y., Duff, K., & Davies, P. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01879.x · Cited by 722 · see citing works
SUMO Modification of Huntingtin and Huntington's Disease Pathology
Steffan, J. S., Agrawal, N., Pallos, J., Rockabrand, E., Trotman, L. C., Slepko, N., Illes, K., Lukácsovich, T., Zhu, Y., Cattaneo, E. F., et al. (2004) · Science · doi:10.1126/science.1092194 · Cited by 713 · see citing works
Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synuclein
Tu, P., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. ‐. (1998) · Annals of Neurology · doi:10.1002/ana.410440324 · Cited by 686 · see citing works
Development of the Proteasome Inhibitor Velcade™ (Bortezomib)
Adams, J., & Kauffman, M. G. (2004) · Cancer Investigation · doi:10.1081/cnv-120030218 · Cited by 656 · see citing works
Altered proteasomal function in sporadic Parkinson’s disease
St. P. McNaught, K., Belizaire, R., Isacson, O., Jenner, P., & Olanow, C. W. (2003) · Experimental Neurology · doi:10.1006/exnr.2002.8050 · Cited by 573 · see citing works
Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer's Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes
Lippa, C. F., Fujiwara, H., Mann, D. M. A., Giasson, B., Baba, M., Schmidt, M. L., Nee, L. E., O'Connell, B., Pollen, D. A., St. George-Hyslop, P., et al. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65722-7 · Cited by 533 · see citing works
Identification of oligomers at early stages of tau aggregation in Alzheimer's disease
Lasagna‐Reeves, C. A., Castillo‐Carranza, D. L., Sengupta, U., Sarmiento, J., Troncoso, J., Jackson, G. R., & Kayed, R. (2012) · The FASEB Journal · doi:10.1096/fj.11-199851 · Cited by 527 · see citing works
Self-citation
Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β
Hoshi, M. M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1237107100 · Cited by 494 · see citing works
Huntingtin and the molecular pathogenesis of Huntington's disease
Landles, C., & Bates, G. P. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400250 · Cited by 485 · see citing works
Accumulation of Pathological Tau Species and Memory Loss in a Conditional Model of Tauopathy
Berger, Z., Roder, H. M., Hanna, A., Carlson, A. M., Rangachari, V., Yue, M., Wszołek, Z. K., Ashe, K. H., Knight, J. A., Dickson, D. W., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0587-07.2007 · Cited by 485 · see citing works
Proteasome 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
The Synaptic Accumulation of Hyperphosphorylated Tau Oligomers in Alzheimer Disease Is Associated With Dysfunction of the Ubiquitin-Proteasome System
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
Eukaryotic Proteasomes Cannot Digest Polyglutamine Sequences and Release Them during Degradation of Polyglutamine-Containing Proteins
Venkatraman, P., Wetzel, R. B., Tanaka, M., Nukina, N., & Goldberg, A. L. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00151-0 · Cited by 424 · see citing works
Molecular Mechanisms of Amyloid Oligomers Toxicity
Kayed, R., & Lasagna‐Reeves, C. A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129001 · Cited by 417 · see citing works
Self-citation
Ubiquitin, cellular inclusions and their role in neurodegeneration
Alves-Rodrigues, A., Gregori, L., & Figueiredo-Pereira, M. E. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01276-4 · Cited by 393 · 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
Phosphorylation of Tau at Both Thr 231 and Ser 262 Is Required for Maximal Inhibition of Its Binding to Microtubules
Sengupta, A., Kabat, J., Novak, M., Wu, Q., Grundke-Iqbal, I., & Iqbal, K. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0813 · Cited by 363 · see citing works
Huntingtin Is Ubiquitinated and Interacts with a Specific Ubiquitin-conjugating Enzyme
Kalchman, M. A., Graham, R. K., Xia, G., Koide, H., Hodgson, J. G., Graham, K. C., Goldberg, Y. P., Gietz, R. D., Pickart, C. M., & Hayden, M. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19385 · Cited by 363 · see citing works
Inhibition of the ubiquitin-proteasome system in Alzheimer's disease
Lam, Y. A., Pickart, C. M., Alban, A., Landon, M., Jamieson, C. J., Ramage, R., Mayer, R. J., & Layfield, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170173897 · Cited by 325 · see citing works
Small 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
Tau pathophysiology in neurodegeneration: a tangled issue
Spires‐Jones, T. L., Stoothoff, W. H., de Calignon, A., Jones, P., & Hyman, B. T. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2008.11.007 · Cited by 316 · see citing works
β-Amyloid Accumulation Impairs Multivesicular Body Sorting by Inhibiting the Ubiquitin-Proteasome System
Almeida, C. G., Takahashi, R. H., & Gouras, G. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5078-05.2006 · Cited by 316 · see citing works
Distinct and Overlapping Sets of SUMO-1 and SUMO-2 Target Proteins Revealed by Quantitative Proteomics
Vertegaal, A. C. O., Andersen, J., Ogg, S. C., Hay, R. T., Mann, M., & Lamond, A. I. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600212-mcp200 · Cited by 314 · see citing works
Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles
Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · cited 1× · see citing works
“Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. in disease progression and validate tau oligomers as a potential drug target (Castillo-Carranza et al., 2013, 2014a,b).”
BackgroundSelf-citation
The Ubiquitin-Proteasome System and Its Role in Inflammatory and Autoimmune Diseases
Jingsong, Wang, Michael, & Maldonado (2006) · 中国免疫学杂志：英文版 · Cited by 269 · see citing works
Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo
Umeda, T., Tomiyama, T., Sakama, N., Tanaka, S., Lambert, M. P., Klein, W. L., & Mori, H. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22640 · Cited by 264 · see citing works
Hyperphosphorylation of tau in PHF.
Morishima-kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Watanabe, A., Titani, K., & Ihara, Y. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00027-c · Cited by 238 · see citing works
Bortezomib (Velcade?) in the treatment of multiple myeloma
Field-Smith, A., Morgan, G. J., & Davies, F. E. (2006) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.2006.2.3.271 · Cited by 236 · see citing works
Huntington's disease is a four-repeat tauopathy with tau nuclear rods
Fernández-Nogales, M., Cabrera, J. R., Santos-Galindo, M., Hoozemans, J. J. M., Ferrer, I., Rozemuller, A. J. M., Hernández, F., Avila, J., & Lucas, J. J. (2014) · Nature Medicine · doi:10.1038/nm.3617 · Cited by 231 · see citing works
Mechanisms of Protein Seeding in Neurodegenerative Diseases
Walker, L. C., Diamond, M. I., Duff, K. E., & Hyman, B. T. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1453 · Cited by 226 · see citing works
Ubiquitin–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
Cellular co-localization of phosphorylated tau- and NACP/α-synuclein-epitopes in Lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies
Arima, K., Hirai, S., Sunohara, N., Aoto, K., Izumiyama, Y., Uéda, K., Ikeda, K., & Kawai, M. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01848-x · Cited by 209 · see citing works
The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases.
Wang, J., & Maldonado, M. A. (2006) · PubMed · Cited by 207 · see citing works
Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Holmes, B. B., & Diamond, M. I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.549295 · Cited by 202 · see citing works
Alpha-synuclein and transgenic mouse models
Fernagut, P., & Chesselet, M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.07.001 · Cited by 199 · see citing works
Mutual interactions between the SUMO and ubiquitin systems: a plea of no contest
Ulrich, H. D. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.08.002 · Cited by 198 · see citing works
Tau protein: Relevance to Parkinson's disease
Lei, P., Ayton, S., Finkelstein, D. I., Adlard, P. A., Masters, C. L., & Bush, A. I. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.07.016 · Cited by 193 · see citing works
Distinct In Vivo Dynamics of Vertebrate SUMO Paralogues
Ayaydin, F., & Dasso, M. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-07-0589 · Cited by 185 · see citing works
SUMOylation and deSUMOylation at a glance
Wang, Y., & Dasso, M. (2009) · Journal of Cell Science · doi:10.1242/jcs.050542 · Cited by 183 · see citing works
Pathological Interface Between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies
Sengupta, U., Guerrero‐Munoz, M. J., Castillo‐Carranza, D. L., Lasagna‐Reeves, C. A., Gerson, J. E., Paulucci-Holthauzen, A. A., Krishnamurthy, S., Farhed, M., Jackson, G. R., & Kayed, R. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.12.019 · Cited by 181 · see citing works
Self-citation
Specific Targeting of Tau Oligomers in Htau Mice Prevents Cognitive Impairment and Tau Toxicity Following Injection with Brain-Derived Tau Oligomeric Seeds
Castillo‐Carranza, D. L., Gerson, J. E., Sengupta, U., Guerrero‐Munoz, M. J., Lasagna‐Reeves, C. A., & Kayed, R. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132477 · Cited by 180 · see citing works
Self-citation
SUMO and transcriptional regulation
Girdwood, D., Tatham, M. H., & Hay, R. T. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2003.12.001 · Cited by 165 · see citing works
Structure of Tetraubiquitin Shows How Multiubiquitin Chains Can Be Formed
Cook, W. J., Jeffrey, L. C., Kasperek, E. M., & Pickart, C. M. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1169 · Cited by 156 · see citing works
Protein quality control in Alzheimer's disease by the ubiquitin proteasome system
de Vrij, F. M. S., Fischer, D. F., VANLEEUWEN, F., & Hol, E. M. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.10.001 · Cited by 152 · see citing works
Autophagy: More Than a Nonselective Pathway
Reggiori, F., Komatsu, M., Finley, K. D., & Simonsen, A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/219625 · Cited by 152 · see citing works
Targeting autophagy in neurodegenerative diseases
Vidal, R. L., Matus, S., Bargsted, L., & Hetz, C. A. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.09.002 · Cited by 145 · see citing works
Sumoylation and human disease pathogenesis
Sarge, K. D., & Park-Sarge, O.-K. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.01.004 · Cited by 143 · see citing works
Formation and Propagation of Tau Oligomeric Seeds
Gerson, J. E., & Kayed, R. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00093 · Cited by 137 · see citing works
Self-citation
Mechanism of Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies
Alonso, A. D. C., Li, B., Grundke, I., & Iqbal, K. (2008) · Current Alzheimer Research · doi:10.2174/156720508785132307 · Cited by 128 · see citing works
Evidence that Non-Fibrillar Tau Causes Pathology Linked to Neurodegeneration and Behavioral Impairments
Brunden, K. R., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14406 · Cited by 125 · see citing works
The Proteasome-Associated Deubiquitinating Enzyme Usp14 Is Essential for the Maintenance of Synaptic Ubiquitin Levels and the Development of Neuromuscular Junctions
Chen, P.-C., Qin, L.-N., Li, X. M., Walters, B. J., Wilson, J. A., Mei, L., & Wilson, S. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2635-09.2009 · Cited by 119 · see citing works
SUMO-1 Modification Alters ADAR1 Editing Activity
Desterro, J. M. P., Keegan, L. P., Jaffray, E., et al. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-06-0536 · Cited by 119 · 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
Interactions of Amyloidogenic Proteins
Giasson, B. I., Lee, V. M. ‐., & Trojanowski, J. Q. (2003) · NeuroMolecular Medicine · doi:10.1385/nmm:4:1-2:49 · Cited by 106 · see citing works
Therapeutic approaches against common structural features of toxic oligomers shared by multiple amyloidogenic proteins
Guerrero‐Munoz, M. J., Castillo‐Carranza, D. L., & Kayed, R. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.023 · Cited by 103 · see citing works
Self-citation
Characterization of tau oligomeric seeds in progressive supranuclear palsy
Gerson, J. E., Sengupta, U., Lasagna‐Reeves, C. A., Guerrero‐Munoz, M. J., Troncoso, J. C., & Kayed, R. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-73 · Cited by 95 · see citing works
Self-citation
Tau aggregation into fibrillar polymers: taupathies
Ávila, J. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01676-8 · Cited by 94 · see citing works
Ubiquitin Homeostasis Is Critical for Synaptic Development and Function
Chen, P., Bhattacharyya, B. J., Hanna, J. W., Minkel, H. R., Wilson, J. A., Finley, D. J., Miller, R. J., & Wilson, S. M. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2922-11.2011 · Cited by 94 · see citing works
Abnormal Interaction of Oligomeric Amyloid-β with Phosphorylated Tau: Implications to Synaptic Dysfunction and Neuronal Damage
Mańczak, M., & Reddy, P. H. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130275 · Cited by 88 · see citing works
Tau Aggregates: Toxic, Inert, or Protective Species?
Bretteville, A., & Planel, E. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14411 · Cited by 87 · see citing works
SUMO-1 immunoreactivity co-localizes with phospho-Tau in APP transgenic mice but not in mutant Tau transgenic mice
Takahashi, K., Ishida, M., Komano, H., & Takahashi, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.012 · Cited by 75 · see citing works
Alzheimer disease: correlation of cerebro-spinal fluid and brain ubiquitin levels
Kudo, T., Iqbal, K., Ravid, R., Swaab, D. F., & Grundke, I. (1994) · Brain Research · doi:10.1016/0006-8993(94)91757-4 · Cited by 75 · see citing works
Role of Ubiquitin Carboxy Terminal Hydrolase-L1 in Neural Cell Apoptosis Induced by Ischemic Retinal Injury in Vivo
Harada, T., Harada, C., Wang, Y.-L., Osaka, H., Amanai, K., Tanaka, K., Takizawa, S., Setsuie, R., Sakurai, M., Sato, Y., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63096-9 · Cited by 73 · see citing works
Advances in Therapeutics for Neurodegenerative Tauopathies: Moving toward the Specific Targeting of the Most Toxic Tau Species
Gerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 73 · see citing works
Self-citation
Alzheimer's disease meets the ubiquitin–proteasome system
Song, S., & Jung, Y. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.005 · Cited by 65 · see citing works
Neuronal Ubiquitin Homeostasis
Hallengren, J. J., Chen, P., & Wilson, S. M. (2013) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-013-9634-4 · Cited by 62 · see citing works
From genetics to pathology: tau and a–synuclein assemblies in neurodegenerative diseases
Goedert, M., Spillantini, M. G., Serpell, L. C., Berriman, J. A., Smith, M. J., Jakes, R., & Crowther, R. A. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2000.0767 · Cited by 57 · see citing works
Proteasome inhibition and Tau proteolysis: an unexpected regulation
Delobel, P., Leroy, O., Hamdane, M., Sambo, A., Delacourte, A., & Buée, L. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.11.018 · Cited by 55 · see citing works
A New Take on Tau
Marx, J. L. (2007) · Science · doi:10.1126/science.316.5830.1416 · Cited by 51 · see citing works
SnapShot: Pathobiology of Alzheimer's Disease
Selkoe, D. J. (2013) · Cell · doi:10.1016/j.cell.2013.07.003 · Cited by 46 · see citing works
Endosome-Lysosomes, Ubiquitin and Neurodegeneration
Mayer, R. J., Tipler, C., Arnold, J., László, L., Al-Khedhairy, A. A., Lowe, J. S., & Landon, M. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0335-0_33 · Cited by 46 · see citing works
Ubiquitin proteasome system in Parkinson's disease: A keeper or a witness?
Martins-Branco, D. A., Esteves, A. R., Santos, D., Arduíno, D. M., Swerdlow, R. H., Oliveira, C. R., Januário, C., & Cardoso, S. M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.08.008 · Cited by 44 · see citing works
Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin
Ubhi, K. K., Rockenstein, E. M., Doppler, E., Mante, M., Adame, A., Patrick, C., Trejo, M., Crews, L. A., Paulino, A., Moessler, H., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0505-4 · Cited by 42 · see citing works
Increased levels of total tau protein in the cerebrospinal fluid in Huntington’s disease
Constantinescu, R., Romer, M., Zetterberg, H., Rosengren, L., & Kieburtz, K. D. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.06.010 · Cited by 40 · see citing works
Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP
Metcalfe, M., Huang, Q., & Figueiredo‐Pereira, M. E. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.70 · Cited by 38 · see citing works
Ubiquitin-reactive neurites in cerebral cortex of subjects with Huntington's chorea: a pathological correlate of dementia?
Cammarata, S., Caponnetto, C., & Tabaton, M. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90448-t · Cited by 33 · see citing works
Tau aggregates as immunotherapeutic targets.
Castillo-Carranza, D. L., Lasagna-Reeves, C., & Kayed, R. (2013) · Frontiers in Bioscience · doi:10.2741/s381 · Cited by 33 · see citing works
Self-citation
Affinity chromatography of native SUMO proteins using His-tagged recombinant UBC9 bound to Co2+-charged talon resin
Bohren, K. M., Gabbay, K. H., & Owerbach, D. (2007) · Protein Expression and Purification · doi:10.1016/j.pep.2007.03.013 · Cited by 26 · see citing works
An honorable compromise regarding amyloid in Alzheimer disease
Terry, R. D. (2001) · Annals of Neurology · doi:10.1002/ana.1042 · Cited by 26 · see citing works
MEL-18 Interacts with HSF2 and the SUMO E2 UBC9 to Inhibit HSF2 Sumoylation
Zhang, J., Goodson, M. L., Hong, Y., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707122200 · Cited by 23 · see citing works
Neocortical changes in Parkinson's disease, revisited.
Sugiyama, H., Hainfellner, J. A., Yoshimura, M., et al. (1994) · PubMed · Cited by 21 · see citing works
Intracellular Aβ and C99 aggregates induce mitochondria-dependent cell death in human neuroglioma H4 cells through recruitment of the 20S proteasome subunits
Park, H., Kim, S.-S., Kang, S., & Rhim, H. (2009) · Brain Research · doi:10.1016/j.brainres.2009.04.001 · Cited by 19 · see citing works
Ubiquitinated dystrophic neurites suggest corticospinal derangement in patients with amyotrophic lateral sclerosis
Schiffer, D., Attanasio, A., Chiò, A., Migheli, A., & Pezzulo, T. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90904-0 · Cited by 15 · see citing works
Failure to find mutations in ubiquitin carboxy-terminal hydrolase L1 gene in familial Parkinson's disease
Zhang, J., Hattori, N., Giladi, N., et al. (2000) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(00)00022-5 · Cited by 12 · see citing works
Cerebral soluble ubiquitin is increased in patients with Alzheimer's disease.
Taddei, N., Liguri, G., Sorbi, S., Amaducci, L., Camici, G. G., Nassi, P., Cecchi, C., & Ramponi, G. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90010-i · Cited by 8 · see citing works
Untitled work
Mattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1

Flagged first, then by citations

Research works printed but not linked: 1

Lasagna-Reeves CA Castillo-Carranza DL Sengupta U Sarmiento J Troncoso J Jackson GR Kayed R Identification of oligomers at early stages of tau aggregation in Alzheimer’s disease FASEB J 2012b 26 1946 1959 22253473 PMC4046102

Sorted by citations

Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
Roles 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
Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases
Kubben, N., & Misteli, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.68 · Cited by 320 · see citing works
Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models
Silva, M. C., Ferguson, F. M., Cai, Q., Donovan, K. A., Nandi, G., Patnaik, D., Zhang, T., Huang, H.-T., Lucente, D. E., Dickerson, B. C., et al. (2019) · eLife · doi:10.7554/elife.45457 · Cited by 283 · see citing works
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway
Dong, C., Zhang, H., Li, L., Tempel, W., Loppnau, P., & Min, J. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0036-1 · Cited by 111 · see citing works
Mutations in Proteasome-Related Genes Are Associated with Thyroid Hemiagenesis
Budny, B., Szczepanek-Parulska, E., Zemojtel, T., Szaflarski, W., Rydzanicz, M., Wesoly, J., Handschuh, L., Wolinski, K., Piatek, K., Niedziela, M., et al. (2017) · Endocrine · doi:10.1007/s12020-017-1287-4 · Cited by 22 · see citing works

Concept and application of circulating proteasomes
Choi, W. H., Kim, S., Park, S., & Lee, M. J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00692-x · Cited by 27 · see citing works
The Effects of Aging on Proteasome Activity, Assembly, and Abundance in C. elegans
Joyce, D. (2012) · eScholarship (California Digital Library)
The effects of aging on proteasome activity, assembly, and abundance in C. elegans - eScholarship
Joyce, D. (2012)
A common mechanism of proteasome impairment by neurodegenerative disease-associated oligomers
Thibaudeau, T. A., Anderson, R. T., & Smith, D. M. (2018) · Nature Communications · doi:10.1038/s41467-018-03509-0 · Cited by 356 · see citing works
Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination
Wen, J.-H., He, X., Feng, Z.-S., Li, D.-Y., Tang, J., & Liu, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108593 · Cited by 81 · see citing works

Authors: Deger, J. M., Gerson, J. E., & Kayed, R.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Corresponding author: Gerson, Julia E.
Kayed, Rakez
ORCID: Deger, Jennifer M.
Gerson, Julia E.
Kayed, Rakez
Venue: Aging Cell
Publisher: Wiley
Published: 2015-06-05
Volume: 14
Issue: 5
Pages: 715-724
ISSN: 1474-9718 (ISSN-L)
1474-9726
DOI: 10.1111/acel.12359
PMC: PMC4568959
OpenAlex: W2142423680
Cited by: 69
References: 111
Citations by year: 2026: 3 · 2025: 3 · 2024: 8 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 2
FWCI: 1.15
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Aging Cell (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
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: proteasome impairment, protein oligomers, neurodegeneration, tau protein, SUMOylation, ubiquitination, amyloidogenic proteins, tau oligomers, Alzheimer's disease, Parkinson's disease, protein degradation, covalent modification, alpha-synuclein, amyloid-beta
MeSH terms: Animals, Humans, Models, Molecular, tau Proteins, Neurodegenerative Diseases, Proteasome Endopeptidase Complex, Proteolysis

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

The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks