TDP‐43 loss of function increases TFEB activity and blocks autophagosome–lysosome fusion
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by selective loss of motor neurons in brain and spinal cord. TAR DNA-binding protein 43 (TDP-43) was identified as a major component of disease pathogenesis in ALS, frontotemporal lobar degeneration (FTLD), and other neurodegenerative disease. Despite the fact that TDP-43 is a multi-functional protein involved in RNA processing and a large number of TDP-43 RNA targets have been discovered, the initial toxic effect and the pathogenic mechanism underlying TDP-43-linked neurodegeneration remain elusive. In this study, we found that loss of TDP-43 strongly induced a nuclear translocation of TFEB, the master regulator of lysosomal biogenesis and autophagy, through targeting the mTORC1 key component raptor. This regulation in turn enhanced global gene expressions in the autophagy-lysosome pathway (ALP) and increased autophagosomal and lysosomal biogenesis. However, loss of TDP-43 also impaired the fusion of autophagosomes with lysosomes through dynactin 1 downregulation, leading to accumulation of immature autophagic vesicles and overwhelmed ALP function. Importantly, inhibition of mTORC1 signaling by rapamycin treatment aggravated the neurodegenerative phenotype in a TDP-43-depleted Drosophila model, whereas activation of mTORC1 signaling by PA treatment ameliorated the neurodegenerative phenotype. Taken together, our data indicate that impaired mTORC1 signaling and influenced ALP may contribute to TDP-43-mediated neurodegeneration.
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TARDBP downregulation promotes TFEB nuclear localization and TFEB target gene expression, but also reduces DCTN1 expression, thereby blocking autolysosome formation and impairing autophagic flux.
“TARDBP downregulation promotes TFEB nuclear localization and TFEB target gene expression, but it also reduces DCTN1 (dynactin subunit 1) expression, thereby blocking autolysosome formation and impairing autophagic flux [350].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [350]
Autophagy dysfunction is linked to TARDBP pathology in ALS.
“Together, these findings link autophagy dysfunction to TARDBP pathology in ALS”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [350]
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BackgroundInfluentialTDP-43 proteinopathy and mitochondrial abnormalities in neurodegeneration
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“, 2011), autophagy (Bose et al., 2011; Xia et al., 2016), endocytosis (Liu et al.”
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Stress granules at the intersection of autophagy and ALS
Monahan, Z. T., Shewmaker, F. P., & Pandey, U. B. (2016) · Brain Research · doi:10.1016/j.brainres.2016.05.022 · Cited by 105 · see citing works
“It has been suggested that TDP-43 is involved in regulating autophagy in general and particularly autophagosomal and lysosomal biogenesis (Bose et al., 2011; Filimonenko et al., 2007; Xia et al., 2016; Ying et al., 2016).”
BackgroundATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome–lysosome fusion
Wang, R., Tan, J., Chen, T., Han, H., Tian, R., Tan, Y., Wu, Y., Cui, J., Chen, F., Li, J., et al. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201804165 · Cited by 108 · see citing works
“Mutations in some of these genes cause human diseases, suggesting that APS– LYS fusion is essential for completion of productive autophagy (Hasegawa et al., 2016; Wang et al., 2016; Xia et al., 2016).”
BackgroundMolecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD
Wood, A., Gurfinkel, Y., Polain, N., Lamont, W. G., & Rea, S. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094705 · Cited by 101 · see citing works
“The effects of TDP-43 knockdown on autophagy were shown to be mTORdependent (TFEB regulation) and mTOR-independent (fusion) [122].”
BackgroundInfluentialDCTN1-related neurodegeneration: Perry syndrome and beyond
Konno, T., Ross, O. A., Teive, H. A. G., Sławek, J. W., Dickson, D. W., & Wszołek, Z. K. (2017) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.06.004 · Cited by 99 · see citing works
Protein Modification and Autophagy Activation
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Self-citationAmyotrophic Lateral Sclerosis and Autophagy: Dysfunction and Therapeutic Targeting
Amin, A., Perera, N. D., Beart, P. M., Turner, B. J., & Shabanpoor, F. (2020) · Cells · doi:10.3390/cells9112413 · Cited by 96 · see citing works
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Autophagy and Its Impact on Neurodegenerative Diseases: New Roles for TDP-43 and C9orf72
Budini, M., Buratti, E., Morselli, E., & Criollo, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00170 · Cited by 91 · see citing works
“Thus, TDP-43 down-regulation decreases Dynactin 1 protein levels and, as consequence, it impairs autophagosome-lysosome fusion (Xia et al., 2016).”
BackgroundInfluentialTDP‐43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons
Schwenk, B. M., Hartmann, H., Serdaroglu, A., Schludi, M. H., Hornburg, D., Meissner, F., Orozco, D., Colombo, A. V., Tahirović, S., Michaelsen, M., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201694221 · Cited by 90 · see citing works
“Moreover, we noticed slightly increased motility of lysosomes, which might relate to the autophagosome – lysosome fusion problems observed in TDP-43-knockdown cell lines recently (Xia et al , 2015).”
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Self-citationProteostasis impairment in ALS
Ruegsegger, C., & Saxena, S. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.032 · Cited by 82 · see citing works
Proteotoxicity and Neurodegenerative Diseases
Ruz, C., Alcantud, J. L., Montero, F. V., Durán, R., & Bandrés‐Ciga, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165646 · Cited by 81 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Impairment of Lysosome Function and Autophagy in Rare Neurodegenerative Diseases
Darios, F. D., & Stévanin, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.033 · Cited by 77 · see citing works
TFEB Biology and Agonists at a Glance
Chen, M., Dai, Y., Liu, S., Fan, Y., Ding, Z.-X., & Li, D. (2021) · Cells · doi:10.3390/cells10020333 · Cited by 73 · see citing works
Uversky, V. N. (2017) · Autophagy · doi:10.1080/15548627.2017.1384889 · Cited by 76 · see citing works
“blocked by TARDBP loss of function.(648) Also, TARDBP targets”
BackgroundPeng, A. Y. T., Agrawal, I., Ho, W. Y., Yen, Y.-C., Pinter, A. J., Liu, J., Phua, Q. X. C., Koh, K. B., Chang, J., Sanford, E., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2007806117 · Cited by 76 · see citing works
“Although TDP-43 was originally described to harbor transcription repressor activity (12), the functions of TDP-43 has since been expanded to include a wide range of biological processes (7, 13–15), including biogenesis and processing of coding and noncoding RNAs (7, 13–15), mRNA transport (16), translation (17, 18), m…”
BackgroundTDP-43 pathology: From noxious assembly to therapeutic removal
Keating, S. S., Gil, R. S., Swanson, M. E. V., Scotter, E. L., & Walker, A. K. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102229 · Cited by 74 · see citing works
Impaired protein degradation in FTLD and related disorders
Götzl, J. K., Lang, C. M., Haass, C., & Capell, A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.008 · Cited by 70 · see citing works
Genetic strategies to tackle neurological diseases in fruit flies
Şentürk, M., & Bellen, H. J. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.017 · Cited by 71 · see citing works
TDP-43 controls lysosomal pathways thereby determining its own clearance and cytotoxicity
Leibiger, C., Deisel, J., Aufschnaiter, A., Ambros, S., Tereshchenko, M., Verheijen, B. M., Büttner, S., & Braun, R. J. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy066 · Cited by 68 · see citing works
Pleiotropic requirements for human TDP-43 in the regulation of cell and organelle homeostasis
Roczniak-Ferguson, A., & Ferguson, S. M. (2019) · Life Science Alliance · doi:10.26508/lsa.201900358 · Cited by 69 · see citing works
“Efforts to define TDP-43 function through genetic depletion approaches have previously been implemented in mice as well as in human cells in culture (Chiang et al., 2010; Kraemer et al., 2010; Ling et al., 2015; Prpar Mihevc et al., 2016; Sephton et al., 2010; Stalekar et al., 2015; Wu et al., 2010; Xia et al., 2016).”
BackgroundHuang, C., Yan, S., & Zhang, Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00219-w · Cited by 71 · see citing works
SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy regulation
Richard, P., Feng, S., Tsai, Y.-L., Li, W., Rinchetti, P., Muhith, U., Irizarry-Cole, J., Stolz, K., Sanz, L. A., Hartono, S. R., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1796292 · Cited by 68 · see citing works
Nuclear miR-30b-5p suppresses TFEB-mediated lysosomal biogenesis and autophagy
Guo, H., Pu, M., Tai, Y., Chen, Y., Lu, H., Qiao, J., Wang, G., Chen, J., Qi, X., Huang, R., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0602-4 · Cited by 64 · see citing works
Self-citationChen, Y., Wang, H., Ying, Z., & Gao, Q. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.03.051 · Cited by 63 · see citing works
Self-citationMao, D., Lin, G., Tepe, B., Zuo, Z., Tan, K. L., Şentürk, M., Zhang, S., Arenkiel, B. R., Sardiello, M., & Bellen, H. J. (2019) · Autophagy · doi:10.1080/15548627.2019.1580103 · Cited by 58 · see citing works
“Loss of TARDBP was recently reported to elevate the levels of TFEB and impair the fusion of autophagosomes with lysosomes [19].”
BackgroundIs amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease?
Deng, Z., Sheehan, P., Chen, S., & Yue, Z. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0232-6 · Cited by 61 · see citing works
“However, a recent report showed that loss of TDP-43 increased the biogenesis of autophagosomes and lysosomes by inhibiting mTORC1 activity and enhancing TFEB activity while also disrupting the fusion of autophagosomes and lysosomes [103].”
BackgroundProtein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum
Shahheydari, H., Ragagnin, A., Walker, A. K., Toth, R. P., Vidal, M., Jagaraj, C. J., Perri, E. R., Konopka, A., Sultana, J. M., & Atkin, J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00119 · Cited by 59 · see citing works
“However, loss of TDP-43 impaired autophagosome-lysosome fusion, potentially affecting cellular protein clearance (Xia et al., 2016).”
BackgroundImplications of Selective Autophagy Dysfunction for ALS Pathology
Vicencio, E., Beltrán, S., Labrador, L., Manque, P., Nassif, M., & Woehlbier, U. (2020) · Cells · doi:10.3390/cells9020381 · Cited by 58 · see citing works
“A strong connection between the mechanisms of ALS and autophagy, independent of the presence of protein aggregates, is the regulation of the expression of autophagic genes, produced by RBP associated with ALS [169].”
BackgroundTranscription factor EB: an emerging drug target for neurodegenerative disorders
Song, J., Liu, J., Jiang, Y., Wang, Z., & Li, M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.10.013 · Cited by 59 · see citing works
Finding the Middle Ground for Autophagic Fusion Requirements
Corona, A. K., & Jackson, W. T. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.07.001 · Cited by 56 · see citing works
Wang, Y., Liu, F.-T., Wang, Y., Guan, R., Chen, C., Li, D.-K., Bu, L.-L., Song, J., Yang, Y., Dong, Y., et al. (2018) · Neurotoxicity Research · doi:10.1007/s12640-018-9865-7 · Cited by 53 · see citing works
“Importantly, they found that simple modulation of mTOR activity by treatment with rapamycin and phosphatidic acid could actually exacerbate neurotoxicity on the neurodegenerative phenotypes of TBPH (Drosophila TDP-43)-depleted flies (Xia et al. 2016).”
BackgroundTRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis
Wang, W., Xia, Z., Farré, J., & Subramani, S. E. (2018) · Autophagy · doi:10.1080/15548627.2018.1463120 · Cited by 53 · see citing works
“The cDNA was used as template for real-time PCR analysis with Fast SYBR Green (Thermo Fisher Scientific, 4,385,612) of target gene expression with the specific primers as listed in Table S1 and as described previously [36,61].”
MethodTsalikis, J., Abdel‐Nour, M., Farahvash, A., Sorbara, M. T., Poon, S., Philpott, D. J., & Girardin, S. E. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00489-18 · Cited by 53 · see citing works
Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
Tamaki, Y., & Urushitani, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012508 · Cited by 52 · see citing works
Wang, M., Wang, H., Tao, Z., Qin, X., Hao, Z., Prehn, J. H. M., Zhen, X., Wang, G., & Ying, Z. (2020) · Aging Cell · doi:10.1111/acel.13126 · Cited by 51 · see citing works
“…in genetic and preclinical studies, there are numbers of studies that suggest the treatment with general “autophagy inducers” such as rapamycin (mTOR inhibitor) does not help to ameliorate disease progression, or may even exacerbate neurotoxicity as seen in ALS animal models (Xia et al., 2016).”
BackgroundMethodResultInfluentialSelf-citationZhang, Z., Wang, N., Ma, Q., Chen, Y., Li, Y., Zhang, L., Li, Q., Shi, M., Wang, H., & Ying, Z. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0260-6 · Cited by 47 · see citing works
Self-citationTDP-43: A Key Therapeutic Target beyond Amyotrophic Lateral Sclerosis
Palomo, V., Tosat‐Bitrián, C., Nozal, V., Nagaraj, S., Martín‐Requero, Á., & Martı́nez, A. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00026 · Cited by 45 · see citing works
Neuronal VCP loss of function recapitulates FTLD-TDP pathology
Wani, A., Zhu, J., Ulrich, J. D., Eteleeb, A. M., Sauerbeck, A. D., Reitz, S. J., Arhzaouy, K., Ikenaga, C., Yuede, C. M., Pittman, S. K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109399 · Cited by 44 · see citing works
“The co-occurrence of autophago-lysosomal pathology and TDP-43 is a common feature seen in other FTLD-TDPmodel systems such as GRN knockout and even TDP-43 overexpression models (Elia et al., 2019; Werner et al., 2020; Xia et al., 2016).”
BackgroundA critical role of Hrd1 in the regulation of optineurin degradation and aggresome formation
Mao, J., Qin, X., Liu, C., Ying, Z., Wang, H., & Wang, G. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx096 · Cited by 42 · see citing works
Self-citationA behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron disease
Ikenaka, K., Tsukada, Y., Giles, A. C., Arai, T., Nakadera, Y., Nakano, S., Kawai, K., Mochizuki, H., Katsuno, M., Sobue, G., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46642-6 · Cited by 40 · see citing works
Role of BMP receptor traffic in synaptic growth defects in an ALS model
Deshpande, M., Feiger, Z., Shilton, A. K., Luo, C. C., Silverman, E., & Rodal, A. A. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-07-0519 · Cited by 38 · see citing works
“…to recycling endosomes was similar to a previously observed TDP-43– induced general disruption in autophagosome–lysosome traffic in mammalian cells and in Drosophila fat body and heads (Xia et al., 2016), we examined the expression and localization of the autophagy marker Atg8-GFP with Tkv-mCherry.”
BackgroundInfluentialGao, J., Wang, L., Gao, C., Arakawa, H., Perry, G. L., & Wang, X. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165580 · Cited by 38 · see citing works
“Also, despite its likely primary function in RNA processing, TDP-43 exhibits diverse roles in regulating autophagy [46, 47], cell cycle [48, 49], endosomal trafficking [50], mitochondrial bioenergetics [25, 27] and fat metabolism [51].”
BackgroundA quantitative biology approach correlates neuronal toxicity with the largest inclusions of TDP-43
Cascella, R., Bigi, A., Riffert, D. G., Gagliani, M. C., Ermini, E., Moretti, M., Cortese, K., Cecchi, C., & Chiti, F. (2022) · Science Advances · doi:10.1126/sciadv.abm6376 · Cited by 37 · see citing works
Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster
Layalle, S., They, L., Ourghani, S., Raoul, C., & Soustelle, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020904 · Cited by 36 · see citing works
“In both cases, the effects of rapamycin or phosphatic acid were dosedependent [174].”
BackgroundInfluentialHuangfu, N., Wang, Y., Xu, Z., Zheng, W., Tao, C., Li, Z., Hu, Y., & Chen, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.687169 · Cited by 36 · see citing works
Chen, Y., Xu, S., Wang, N., Ma, Q., Peng, P., Yu, Y., Zhang, L., Ying, Z., & Wang, H. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00027-9 · Cited by 35 · see citing works
Self-citationFoster, A., Flynn, L. L., Cluning, C., Cheng, F., Davidson, J. M., Lee, A., Polain, N., Mejzini, R., Farrawell, N. E., Yerbury, J. J., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-90822-2 · Cited by 35 · see citing works
Versluys, L., Pereira, P. E., Schuermans, N., Paepe, B. D., Bleecker, J. D., Bogaert, E., & Dermaut, B. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.815765 · Cited by 34 · see citing works
“Furthermore, in the absence of TDP-43 the fusion between autophagosomes and lysosomes is disrupted, resulting in the presence of autophagic vesicles (Xia et al., 2016).”
BackgroundThe Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer
Ma, X., Ying, Y., Xie, H., Liu, X., Wang, X., & Li, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.755096 · Cited by 33 · see citing works
“Through literature review and the context presented above, the cellular biological events mediated by the TDP-43 network mainly include cell cycle, apoptosis, and autophagy (37, 54, 57, 70).”
BackgroundLysosome quality control in health and neurodegenerative diseases
Ferrari, V., Tedesco, B., Cozzi, M., Chierichetti, M., Casarotto, E., Pramaggiore, P., Cornaggia, L., Mohamed, A. A., Patelli, G., Piccolella, M., et al. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00633-2 · Cited by 33 · see citing works
“The lysosomal toxicity of protein aggregates has been directly TARDBP Toxicity mediated by aggregation and loss of function ALS/FTD [195, 196] MAPT Toxicity mediated by aggregation and loss of function FTD/ALS [199, 200] FUS Toxicity mediated by aggregation ALS [202] IT15 Toxicity mediated by…”
BackgroundKumar, S., Phaneuf, D., & Julien, J. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00952-0 · Cited by 32 · see citing works
“Here, we have determined by immunoblotting of brain extracts the levels of LC3B-II, a marker of autophagosome formation [14].”
Ultrastructural Alterations of Von Economo Neurons in the Anterior Cingulate Cortex in Schizophrenia
Krause, M., Theiß, C., & Brüne, M. (2017) · The Anatomical Record · doi:10.1002/ar.23635 · Cited by 31 · see citing works
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Connecting the dots: Neuronal senescence, stress granules, and neurodegeneration
Ma, Y., & Farny, N. G. (2023) · Gene · doi:10.1016/j.gene.2023.147437 · Cited by 30 · see citing works
Casiraghi, V., Sorce, M. N., Santangelo, S., Invernizzi, S., Bossolasco, P., Lattuada, C., Battaglia, C., Venturin, M., Silani, V., Colombrita, C., et al. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115057 · Cited by 30 · see citing works
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Novel therapeutic approaches to target neurodegeneration
de la Fuente, A. G., Pelucchi, S., Mertens, J., Luca, M. D., Mauceri, D., & Marcello, E. E. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16078 · Cited by 30 · see citing works
Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder
Marchi, F. D., Franjkic, T., Schito, P., Russo, T., Nimac, J., Chami, A. A., Mele, A., Vidatic, L., Križ, J., Julien, J., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11061599 · Cited by 28 · see citing works
Sung, W., Noh, M., Nahm, M., Kim, Y. S., Ki, C., Kim, Y.-E., Kim, H.-J., & Kim, S. H. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03039-1 · Cited by 31 · see citing works
“Loss of nuclear TDP-43 is a key aspect of TDP-43 pathology that may disrupt the autophagy–lysosomal and endolysosomal systems [85–89].”
BackgroundAdvancements and challenges in amyotrophic lateral sclerosis
Bradford, D. R., & Rodgers, K. E. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1401706 · Cited by 28 · see citing works
“…TDP-43 aggregates in the cytoplasm disrupts normal cellular processes, decreasing autophagy (by affecting TFEB [transcription factor EB] localization), increasing stress granule formation, and increases mitochondrial dysfunction (Liu-Yesucevitz et al., 2010; Stribl et al., 2014; Xia et al., 2016).”
BackgroundFu, Y., Zhang, J., Qin, R., Ren, Y., Zhou, T., Han, B., & Liu, B. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100053 · Cited by 28 · see citing works
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Self-citationRepurposing Oxiconazole against Colorectal Cancer via PRDX2-mediated Autophagy Arrest
Shi, J., Zhou, L., Huang, H.-S., Peng, L., Xie, N., Nice, E. C., Fu, L., Jiang, C., & Huang, C. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.70679 · Cited by 27 · see citing works
“Immunoblotting assays were then used to examine the expression of proteins associated with lysosome-autophagosome fusion, including Myosin, SNAP29, Dynactin, Dynein HC and RAB7A [21, 22].”
MethodRecent advances in understanding amyotrophic lateral sclerosis and emerging therapies
Gittings, L. M., & Sattler, R. (2020) · Faculty Reviews · doi:10.12703/b/9-12 · Cited by 26 · see citing works
Aberrant Stress Granule Dynamics and Aggrephagy in ALS Pathogenesis
Zhang, Y., Gu, J., & Sun, Q. (2021) · Cells · doi:10.3390/cells10092247 · Cited by 26 · see citing works
TDP-43 in the spectrum of MND-FTLD pathologies
Heyburn, L., & Moussa, C. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.07.001 · Cited by 26 · see citing works
“…been shown to be dysfunctional in forms of ALS and caused by TARDBP mutations and it has been suggested that TDP-43 is involved in regulation of autophagy by affecting the biogenesis of autophagosomes and lysosomes (Filimonenko et al., 2007; Bose et al., 2011; Xia et al., 2016; Ying et al., 2016).”
BackgroundThe contribution of C. elegans neurogenetics to understanding neurodegenerative diseases
Liang, J., McKinnon, I. A., & Rankin, C. H. (2020) · Journal of Neurogenetics · doi:10.1080/01677063.2020.1803302 · Cited by 25 · see citing works
Bharathi, V., Girdhar, A., & Patel, B. K. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.118993 · Cited by 22 · see citing works
Molecular Chaperones’ Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis
Kinger, S., Dubey, A. R., Kumar, P., Jagtap, Y. A., Choudhary, A., Kumar, A., Prajapati, V. K., Dhiman, R., & Mishra, A. (2023) · Cells · doi:10.3390/cells12091302 · Cited by 24 · see citing works
Jiao, F., Zhou, B., & Meng, L. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13985 · Cited by 21 · see citing works
Santarelli, S., Londero, C., Soldano, A., Candelaresi, C., Todeschini, L., Vernizzi, L., & Bellosta, P. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1082047 · Cited by 23 · see citing works
“Controversial results have been obtained in TARDBP knockout cells, where although the lysosomal transcription factor TFEB is upregulated, accumulation of immature autophagic vesicles and reduced expression of Atg7 are observed, suggesting that reduction of TARDBP affects other signals/genes necessary for a functional…”
BackgroundTanaka, Y., Ito, S.-I., Honma, Y., Hasegawa, M., Kametani, F., Suzuki, G., Kozuma, L., Takeya, K., & Eto, M. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105272 · Cited by 22 · see citing works
“The levels of LC3-II were signi fi cantly increased not only in the cell fraction, as previously reported (49), but also in the P1 and P2 EV fractions (Fig.”
Background
- Authors
- Xia, Q., Wang, H., Hao, Z., Fu, C., Hu, Q., Gao, F., Ren, H., Chen, D., Han, J., Ying, Z., & Wang, G.
- Affiliations
- Soochow University (CN)
- University of Science and Technology of China (CN)
- Southeast University (CN)
- Corresponding author
- Ying, Zheng
- Wang, Guanghui
- ORCID
- Venue
- The EMBO Journal
- Published
- 2015-12-23
- Volume
- 35
- Issue
- 2
- Pages
- 121-142
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4718457
- OpenAlex
- W2264272493
- Cited by
- 195
- References
- 58
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 17 · 2023: 11 · 2022: 20 · 2021: 20 · 2020: 26 · 2019: 25 · 2018: 12 · 2017: 19 · 2016: 8 · 2015: 1
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Sciences Foundation of China (31330030, 81371393, 31200803, 31371072)
- National High‐tech Research and Development program of China 973‐projects (2012CB947602)
- Natural Science Foundation of Jiangsu Province (BK2012181)
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro‐Psycho‐Diseases (BM2013003)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- TDP-43, TFEB, mTORC1, autophagy-lysosome pathway, autophagosome-lysosome fusion, lysosomal biogenesis, neurodegeneration, amyotrophic lateral sclerosis, raptors, rapamycin, Drosophila model
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Amyotrophic Lateral Sclerosis, Animals, Autophagy, Cell Line, DNA-Binding Proteins, Drosophila, HeLa Cells, Humans, Lysosomes, Models, Biological, Cell Line, Tumor, Multiprotein Complexes, Mice, Rats, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Frontotemporal Lobar Degeneration, HEK293 Cells, TOR Serine-Threonine Kinases
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 ›
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