Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain
Open accessAbstract
The brain has a limited capacity to self-protect against protein aggregate-associated pathology, and mounting evidence supports a role for phagocytic glia in this process. We have established a Drosophila model to investigate the role of phagocytic glia in clearance of neuronal mutant huntingtin (Htt) aggregates associated with Huntington disease. We find that glia regulate steady-state numbers of Htt aggregates expressed in neurons through a clearance mechanism that requires the glial scavenger receptor Draper and downstream phagocytic engulfment machinery. Remarkably, some of these engulfed neuronal Htt aggregates effect prion-like conversion of soluble, wild-type Htt in the glial cytoplasm. We provide genetic evidence that this conversion depends strictly on the Draper signalling pathway, unveiling a previously unanticipated role for phagocytosis in transfer of pathogenic protein aggregates in an intact brain. These results suggest a potential mechanism by which phagocytic glia contribute to both protein aggregate-related neuroprotection and pathogenesis in neurodegenerative disease. Phagocytic glia can internalize protein aggregates in vitro. Here Pearce et al. show in Drosophila that glia clear mutant huntingtin (Htt) aggregates in a scavenger receptor Draper-dependent manner in vivo, and that internalized Htt aggregates induce the prion-like conversion of wild-type Htt expressed in the glial cytoplasm.
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
Cites
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?
Glial cells such as microglia and astrocytes perform normal immune functions in the CNS and play a vital role in the spreading of pathological tau.
“Glial cells such as microglia and astrocytes perform normal immune functions in CNS and also play a vital role in the spreading of pathological tau [80, 83].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
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
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
Adams, J., Dinesh, K., Xiong, M., Tarolli, C. G., Sharma, S., Sheth, N., Aranyosi, A. J., Zhu, W. Y., Goldenthal, S. B., Biglan, K., et al. (2017) · Digital Biomarkers · doi:10.1159/000479018 · Cited by 3,190 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689 · see citing works
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
The amyloid state and its association with protein misfolding diseases.
Knowles, T. P. J., Vendruscolo, M., & Dobson, C. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3810 · Cited by 2,382 · see citing works
Huntington's disease: from molecular pathogenesis to clinical treatment
Ross, C. A., & Tabrizi, S. J. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70245-3 · Cited by 1,751 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M.-Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.033 · Cited by 1,569 · see citing works
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903691106 · Cited by 1,485 · see citing works
Reactive Gliosis and the Multicellular Response to CNS Damage and Disease
Burda, J. E., & Sofroniew, M. V. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.034 · Cited by 1,431 · 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
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · see citing works
Propagation of Tau Misfolding from the Outside to the Inside of a Cell
Frost, B., Jacks, R. L., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808759200 · Cited by 1,252 · see citing works
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220 · see citing works
Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease
Yamamoto, A., Lucas, J. J., & Hen, R. (2000) · Cell · doi:10.1016/s0092-8674(00)80623-6 · Cited by 1,068 · 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
Molecular, Anatomical, and Functional Organization of the Drosophila Olfactory System
Couto, A., Alenius, M., & Dickson, B. J. (2005) · Current Biology · doi:10.1016/j.cub.2005.07.034 · Cited by 967 · see citing works
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909 · see citing works
Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds
Holmes, B. B., DeVos, S. L., Kfoury, N., Li, M., Jacks, R., Yanamandra, K., Ouidja, M. O., Brodsky, F. M., Marasa, J., Bagchi, D. P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301440110 · Cited by 859 · see citing works
Microglial Phagocytosis of Live Neurons
Brown, G. C., & Neher, J. J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3710 · Cited by 853 · see citing works
Brain homogenates from human tauopathies induce tau inclusions in mouse brain
Clavaguera, F., Akatsu, H., Fraser, G. M., Crowther, R. A., Frank, S., Hench, J., Probst, A., Winkler, D. T., Reichwald, J., Staufenbiel, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301175110 · Cited by 750 · see citing works
Proteostasis impairment in protein-misfolding and -aggregation diseases
Hipp, M. S., Park, S.-H., & Hartl, F. U. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.05.003 · Cited by 656 · see citing works
Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases
Guo, J. L., & Lee, V. M. Y. (2014) · Nature Medicine · doi:10.1038/nm.3457 · Cited by 641 · see citing works
Engulfment of apoptotic cells: signals for a good meal
Ravichandran, K. S., & Lorenz, U. M. (2007) · Nature reviews. Immunology · doi:10.1038/nri2214 · Cited by 634 · see citing works
Microglial dysfunction in brain aging and Alzheimer's disease
Mosher, K. I., & Wyss-Coray, T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.008 · Cited by 618 · see citing works
Potter, C. J., Tasic, B., Russler-Germain, E. V., Liang, L., & Luo, L. (2010) · Cell · doi:10.1016/j.cell.2010.02.025 · Cited by 605 · see citing works
Self-citationTong, X., Ao, Y., Faas, G. C., Nwaobi, S. E., Xu, J., Haustein, M. D., Anderson, M. A., Mody, I., Olsen, M. L., Sofroniew, M. V., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3691 · Cited by 592 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
The Drosophila Cell Corpse Engulfment Receptor Draper Mediates Glial Clearance of Severed Axons
MacDonald, J. M., Beach, M. G., Porpiglia, E., Sheehan, A. E., Watts, R. J., & Freeman, M. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.028 · Cited by 523 · see citing works
Prion-like Properties of Pathological TDP-43 Aggregates from Diseased Brains
Nonaka, T., Masuda‐Suzukake, M., Arai, T., Hasegawa, Y., Akatsu, H., Obi, T., Yoshida, M., Murayama, S., Mann, D. M. A., Akiyama, H., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.007 · Cited by 520 · see citing works
Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation
Chen, S., Ferrone, F. A., & Wetzel, R. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182276099 · Cited by 519 · see citing works
Markstein, M., Pitsouli, C., Villalta, C., Celniker, S., & Perrimon, N. (2008) · Nature Genetics · doi:10.1038/ng.101 · Cited by 516 · see citing works
Bennett, E. J., Bence, N., Rajadas, J., & Kopito, R. R. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.021 · Cited by 509 · see citing works
Self-citationThe cell biology of receptor-mediated virus entry
Grove, J., & Marsh, M. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201108131 · Cited by 506 · see citing works
Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502 · see citing works
Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity
Shin, J., Fang, Z.-H., Yu, Z.-X., Wang, C.-E., Li, S., & Li, X. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200508072 · Cited by 475 · see citing works
Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells
Münch, C., O’Brien, J., & Bertolotti, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017275108 · Cited by 475 · see citing works
Ahmed, Z., Cooper, J., Murray, T. K., Garn, K., McNaughton, E., Clarke, H., Parhizkar, S., Ward, M. A., Cavallini, A., Jackson, S., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1254-6 · Cited by 460 · see citing works
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455 · see citing works
A Plaque-Specific Antibody Clears Existing β-amyloid Plaques in Alzheimer's Disease Mice
DeMattos, R. B., Lu, J., Tang, Y., Racke, M. M., DeLong, C. A., Tzaferis, J. A., Hole, J. T., Forster, B. M., McDonnell, P. C., Liu, F., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.029 · Cited by 442 · see citing works
Life on the inside: the intracellular lifestyle of cytosolic bacteria
Ray, K., Marteyn, B., Sansonetti, P. J., & Tang, C. M. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2112 · Cited by 423 · see citing works
Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates
Ren, P.-H., Lauckner, J. E., Kachirskaia, I., Heuser, J. E., Melki, R., & Kopito, R. R. (2009) · Nature Cell Biology · doi:10.1038/ncb1830 · Cited by 410 · see citing works
Self-citationRayaprolu, S., Mullen, B., Baker, M., Lynch, T., Finger, E., Seeley, W. W., Hatanpaa, K. J., Lomen-Hoerth, C., Kertesz, A., Bigio, E. H., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-19 · Cited by 404 · see citing works
Freeman, M. R., Delrow, J. J., Kim, J., Johnson, E. A., & Doe, C. Q. (2003) · Neuron · doi:10.1016/s0896-6273(03)00289-7 · Cited by 388 · see citing works
GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo
Bach, E. A., Ekas, L. A., Ayala‐Camargo, A., Flaherty, M. S., Lee, H., Perrimon, N., & Baeg, G. (2006) · Gene Expression Patterns · doi:10.1016/j.modgep.2006.08.003 · Cited by 373 · see citing works
Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms
Bradford, J. W., Shin, J., Redd, M. A., Wang, C.-E., Li, X.-J., & Li, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911503106 · Cited by 362 · see citing works
Meyer, K., Ferraiuolo, L., Miranda, C. J., Likhite, S., McElroy, S., Renusch, S., Ditsworth, D., Lagier-Tourenne, C., Smith, R. A., Ravits, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314085111 · Cited by 345 · see citing works
Antibody-Aided Clearance of Extracellular α-Synuclein Prevents Cell-to-Cell Aggregate Transmission
Bae, E.-J., Lee, H.-J., Rockenstein, E., Ho, D.-H., Park, E.-B., Yang, N.-Y., Desplats, P., Masliah, E., & Lee, S.-J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1292-12.2012 · Cited by 339 · see citing works
Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors
Crotti, A., Benner, C., Kerman, B. E., Gosselin, D., Lagier-Tourenne, C., Zuccato, C., Cattaneo, E., Gage, F. H., Cleveland, D. W., & Glass, C. K. (2014) · Nature Neuroscience · doi:10.1038/nn.3668 · Cited by 333 · see citing works
Awasaki, T., Tatsumi, R., Takahashi, K., Arai, K., Nakanishi, Y., Ueda, R., & Ito, K. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.027 · Cited by 285 · see citing works
<i>TREM2</i>Variant p.R47H as a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis
Cady, J., Koval, E. D., Benitez, B. A., Zaidman, C., Jockel-Balsarotti, J., Allred, P., Baloh, R. H., Ravits, J., Simpson, E., Appel, S. H., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.6237 · Cited by 262 · see citing works
Recovery from Polyglutamine-Induced Neurodegeneration in Conditional <i>SCA1</i> Transgenic Mice
Zu, T., Duvick, L. A., Kaytor, M. D., Berlinger, M. S., Zoghbi, H. Y., Clark, H. B., & Orr, H. T. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2978-04.2004 · Cited by 262 · see citing works
Chatterjee, N., & Bohmann, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034063 · Cited by 254 · see citing works
Hoopfer, E. D., McLaughlin, T., Watts, R. J., Schuldiner, O., O’Leary, D. D. M., & Luo, L. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.013 · Cited by 254 · see citing works
Self-citationTasdemir-Yilmaz, O. E., & Freeman, M. R. (2013) · Genes & Development · doi:10.1101/gad.229518.113 · Cited by 254 · see citing works
Transfer of polyglutamine aggregates in neuronal cells occurs in tunneling nanotubes
Costanzo, M., Abounit, S., Marzo, L., Danckaert, A., Chamoun, Z., Roux, P., & Zurzolo, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.126086 · Cited by 210 · see citing works
Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling
Ziegenfuss, J. S., Biswas, R., Avery, M. A., Hong, K., Sheehan, A. E., Yeung, Y.-G., Stanley, E. R., & Freeman, M. R. (2008) · Nature · doi:10.1038/nature06901 · Cited by 202 · see citing works
Mutant huntingtin is present in neuronal grafts in huntington disease patients
Cicchetti, F., Lacroix, S., Cisbani, G., Vallières, N., Saint‐Pierre, M., St‐Amour, I., Tolouei, R., Skepper, J. N., Hauser, R. A., Mantovani, D., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24174 · Cited by 193 · see citing works
Pecho‐Vrieseling, E., Rieker, C., Fuchs, S., Bleckmann, D., Esposito, M. S., Botta, P., Goldstein, C., Bernhard, M., Galimberti, I., Müller, M. M., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3761 · Cited by 185 · see citing works
Intercellular (Mis)communication in Neurodegenerative Disease
Garden, G. A., & Spada, A. R. L. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.017 · Cited by 170 · see citing works
Indirect inhibition of 26S proteasome activity in a cellular model of Huntington’s disease
Hipp, M. S., Patel, C. N., Bersuker, K., Riley, B. E., Kaiser, S. E., Shaler, T. A., Brandeis, M., & Kopito, R. R. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201110093 · Cited by 168 · see citing works
Self-citationHan, C., Song, Y., Xiao, H., Wang, D., Franc, N. C., Jan, L. Y., & Jan, Y. N. (2014) · Neuron · doi:10.1016/j.neuron.2013.11.021 · Cited by 167 · see citing works
Herber, D. L., Mercer, M., Roth, L. M., Symmonds, K., Maloney, J. L., Wilson, N., Freeman, M. J., Morgan, D., & Gordon, M. N. (2007) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-007-9069-z · Cited by 138 · see citing works
Distinct molecular pathways mediate glial activation and engulfment of axonal debris after axotomy
Ziegenfuss, J. S., Doherty, J., & Freeman, M. R. (2012) · Nature Neuroscience · doi:10.1038/nn.3135 · Cited by 92 · see citing works
Etchegaray, J. I., Timmons, A. K., Klein, A. P., Pritchett, T. L., Welch, E., Meehan, T. L., Li, C., & McCall, K. (2012) · Development · doi:10.1242/dev.082776 · Cited by 92 · see citing works
MacDonald, J. M., Doherty, J., HACKETT, R. J., et al. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.30 · Cited by 78 · see citing works
Roszik, J., Szöllõsi, J., & Vereb, G. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-346 · Cited by 66 · see citing works
Trevino, R., Lauckner, J. E., Sourigues, Y., Pearce, M. M. P., Bousset, L., Melki, R., & Kopito, R. R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.372474 · Cited by 52 · see citing works
Self-citationGong, B., Kielar, C., & Morton, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041450 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Protein misfolding in neurodegenerative diseases: Implications and strategies
Sweeney, P., Park, H., Baumann, M., Dunlop, J., Frydman, J., Kopito, R., McCampbell, A., Leblanc, G., Venkateswaran, A., Nurmi, A., et al. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0077-5 · Cited by 675 · see citing works
Self-citationTau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
“Glial cells such as microglia and astrocytes perform normal immune functions in CNS and also play a vital role in the spreading of pathological tau [80, 83].”
BackgroundElusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
What is the evidence that tau pathology spreads through prion-like propagation?
Mudher, A., Colin, M., Dujardin, S., Medina, M., Dewachter, I., Alavi Naini, S. M., Mandelkow, E.-M., Mandelkow, E., Buée, L., Goedert, M., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0488-7 · Cited by 384 · see citing works
Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs)
Rauch, J. N., Chen, J. J., Sorum, A. W., Miller, G. M., Sharf, T., See, S. K., Hsieh-Wilson, L. C., Kampmann, M., & Kosik, K. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-24904-z · Cited by 211 · see citing works
Mechanisms of protein toxicity in neurodegenerative diseases
Chung, C. G., Lee, H., & Lee, S. B. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2854-4 · Cited by 142 · see citing works
Mutant Huntingtin Is Secreted via a Late Endosomal/Lysosomal Unconventional Secretory Pathway
Trajkovic, K., Jeong, H., & Krainc, D. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0118-17.2017 · Cited by 85 · see citing works
Primary cilia and autophagic dysfunction in Huntington’s disease
Kaliszewski, M., Knott, A. B., & Bossy-Wetzel, E. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.80 · Cited by 55 · see citing works
The Molecular Clock and Neurodegenerative Disease: A Stressful Time
Carter, B., Justin, H. S., Gulick, D., & Gamsby, J. J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.644747 · Cited by 42 · see citing works
The Dichotomous Role of Extracellular Vesicles in the Central Nervous System
Graykowski, D. R., Wang, Y.-Z., Upadhyay, A., & Savas, J. N. (2020) · iScience · doi:10.1016/j.isci.2020.101456 · Cited by 39 · see citing works
- Authors
- Pearce, M. M. P., Spartz, E. J., Hong, W., Luo, L., & Kopito, R. R.
- Affiliations
- Stanford University (US)
- California Institute of Technology (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kopito, Ron R.
- Venue
- Nature Communications
- Published
- 2015-04-13
- Volume
- 6
- Issue
- 1
- Pages
- 6768-6768
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4515032
- OpenAlex
- W2100449855
- Cited by
- 159
- References
- 73
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 12 · 2023: 12 · 2022: 19 · 2021: 17 · 2020: 12 · 2019: 10 · 2018: 17 · 2017: 25 · 2016: 15 · 2015: 11
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- University of Massachusetts Medical School
- National Institute on Deafness and Other Communication Disorders (R01DC005982)
- National Institute of Neurological Disorders and Stroke (NS70420, R01NS042842, F32NS070420)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- huntingtin aggregates, Huntington's disease, glial phagocytosis, protein aggregate clearance, neurodegeneration, Drosophila brain
- MeSH terms
- Huntingtin Protein, Red Fluorescent Protein, Animals, Bacterial Proteins, Brain, Disease Models, Animal, Drosophila melanogaster, Gene Expression Regulation, Humans, Huntington Disease, Luminescent Proteins, Membrane Proteins, Microtubule-Associated Proteins, Mutation, Neuroglia, Neurons, Phagocytosis, Prions, Signal Transduction, Genes, Reporter, Disease Progression, Molecular Mimicry, Drosophila Proteins, Protein Aggregation, Pathological, Protein Aggregates
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
