Optineurin suppression causes neuronal cell death via NF‐κB pathway
Open accessAbstract
Mutations in more than 10 genes are reported to cause familial amyotrophic lateral sclerosis (ALS). Among these genes, optineurin (OPTN) is virtually the only gene that is considered to cause classical ALS by a loss‐of‐function mutation. Wild‐type optineurin (OPTN WT) suppresses nuclear factor‐kappa B (NF‐κB) activity, but the ALS‐causing mutant OPTN is unable to suppress NF‐κB activity. Therefore, we knocked down OPTN in neuronal cells and examined the resulting NF‐κB activity and phenotype. First, we confirmed the loss of the endogenous OPTN expression after si RNA treatment and found that NF‐κB activity was increased in OPTN‐knockdown cells. Next, we found that OPTN knockdown caused neuronal cell death. Then, overexpression of OPTN WT or OPTN E50K with intact NF‐κB‐suppressive activity, but not overexpression of ALS‐related OPTN mutants, suppressed the neuronal death induced by OPTN knockdown. This neuronal cell death was inhibited by withaferin A, which selectively inhibits NF‐κB activation. Lastly, involvement of the mitochondrial proapoptotic pathway was suggested for neuronal death induced by OPTN knockdown. Taken together, these results indicate that inappropriate NF‐κB activation is the pathogenic mechanism underlying OPTN mutation‐related ALS. image Among the genes for typical amyotrophic lateral sclerosis (ALS) phenotypes, optineurin (OPTN) is virtually the only gene in which a loss‐of‐function mutation is considered as the principal disease mechanism. We found that OPTN knockdown induced neuronal cell death via NF‐κB activation. Furthermore, proapoptotic molecules such as p53 and Bax representing downstream targets of NF‐κB are suggested to be involved in neuronal death.
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ALS-associated OPTN mutations may accentuate neuronal loss secondary to neuroinflammation.
“which may accentuate neuronal loss secondary to neuroinflammation [261].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [261]
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Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063 · see citing works
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265 · see citing works
Self-citationAdult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin
Rezaie, T., Child, A. H., Hitchings, R. A., Brice, G. W., MILLER, L. J., Coca‐Prados, M., Héon, E., Krupin, T., Ritch, R. H., Kreutzer, D. L., et al. (2002) · Science · doi:10.1126/science.1066901 · Cited by 1,105 · see citing works
Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis
Sahlender, D. A., Roberts, R. C., Arden, S. D., Spudich, G. M., Taylor, M. J., Luzio, J. P., Kendrick‐Jones, J., & Buß, F. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200501162 · Cited by 426 · see citing works
Gould, T. W., Buss, R. R., Vinsant, S. L., Prevette, D. M., Sun, W., Knudson, C. M., Milligan, C., & Oppenheim, R. W. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2315-06.2006 · Cited by 397 · see citing works
Swarup, V., Phaneuf, D., Dupré, N., Petri, S., Strong, M. J., Križ, J., & Julien, J. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20111313 · Cited by 338 · see citing works
Bail, O. L., Schmidt‐Ullrich, R., & Israël, A. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06197.x · Cited by 314 · see citing works
Yoshihara, T., Ishigaki, S., Yamamoto, M., Liang, Y., Jun, Niwa, I., Takeuchi, H., Doyu, M., & Sobue, G. (2001) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00683.x · Cited by 275 · see citing works
Hensley, K. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00087-1 · Cited by 220 · see citing works
Poloni, M., Facchetti, D., Mai, R., Micheli, A., Agnoletti, L., Francolini, G., Mora, G., Camana, C., Mazzini, L., & Bachetti, T. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01177-0 · Cited by 197 · see citing works
LePage, K. T., DICKEY, R. W., Gerwick, W. H., Jester, E. L. E., & Murray, T. F. (2005) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v17.i1.20 · Cited by 162 · see citing works
Chi, Z.-L., Akahori, M., Obazawa, M., Minami, M., Noda, T., Nakaya, N., Tomarev, S., Kawase, K., Yamamoto, T., Noda, S., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq146 · Cited by 151 · see citing works
p53 Is Abnormally Elevated and Active in the CNS of Patients with Amyotrophic Lateral Sclerosis
Martin, L. J. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0314 · Cited by 135 · see citing works
Cerebral ischemia: gene activation, neuronal injury, and the protective role of antioxidants
Clemens, J. A. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00258-6 · Cited by 130 · see citing works
Optineurin in neurodegenerative diseases
Osawa, T., Mizuno, Y., Fujita, Y., Takatama, M., Nakazato, Y., & Okamoto, K. (2011) · Neuropathology · doi:10.1111/j.1440-1789.2011.01199.x · Cited by 125 · see citing works
Novel optineurin mutations in patients with familial and sporadic amyotrophic lateral sclerosis
Bo, R. D., Tiloca, C., Pensato, V., Corrado, L., Ratti, A., Ticozzi, N., Corti, S. P., Castellotti, B., Mazzini, L., Sorarú, G., et al. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2011.242313 · Cited by 102 · see citing works
Screening of OPTN in French familial amyotrophic lateral sclerosis
Millecamps, S., Boillée, S., Chabrol, E., Camu, W., Cazeneuve, C., Salachas, F., Pradat, P., Danel-Brunaud, V., Vandenberghe, N., Corcia, P., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.11.005 · Cited by 84 · see citing works
Ito, H., Fujita, K., Nakamura, M., Wate, R., Kaneko, S., Sasaki, S., Yamane, K., Suzuki, N., Aoki, M., Shibata, N., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0809-z · Cited by 61 · see citing works
Self-citationAnalysis of OPTN as a causative gene for amyotrophic lateral sclerosis
Belzil, V., Daoud, H., Desjarlais, A., Bouchard, J.-P., Dupré, N., Camu, W., Dion, P. A., & Rouleau, G. A. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.10.001 · Cited by 51 · see citing works
A novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS
Tümer, Z., Bertelsen, B., Gredal, O., Magyari, M., Nielsen, K. C., LuCamp, Grønskov, K., & Brøndum‐Nielsen, K. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.07.001 · Cited by 49 · see citing works
Sippl, C., Bosserhoff, A., Fischer, D., & Tamm, E. R. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.08.011 · Cited by 44 · see citing works
Effects of optineurin siRNA on apoptotic genes and apoptosis in RGC-5 cells.
Li, H., Ao, X., Jia, J., Wang, Q., & Zhang, Z. (2011) · PubMed Central · Cited by 12 · see citing works
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Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies
Beers, D. R., & Appel, S. H. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30394-6 · Cited by 387 · see citing works
ALS Genetics: Gains, Losses, and Implications for Future Therapies
Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.022 · Cited by 370 · see citing works
Inflammation in ALS/FTD pathogenesis
McCauley, M. E., & Baloh, R. H. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-1933-9 · Cited by 316 · see citing works
PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer’s disease
Du, F., Yu, Q., Yan, S., Hu, G., Lue, L., Walker, D., Wu, L., Yan, S. F., Tieu, K., & Yan, S. S. (2017) · Brain · doi:10.1093/brain/awx258 · Cited by 306 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“In addition, ALS-associated OPTN mutations enhance microglial NFKB1 expression [260], which may accentuate neuronal loss secondary to neuroinflammation [261].”
Backgroundp53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR)
Maor-Nof, M., Shipony, Z., Lopez-Gonzalez, R., Nakayama, L., Zhang, Y., Couthouis, J., Blum, J. A., Castruita, P. A., Linares, G. R., Ruan, K., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.025 · Cited by 153 · see citing works
SQSTM1 mutations – Bridging Paget disease of bone and ALS/FTLD
Rea, S. L., Majcher, V., Searle, M. S., & Layfield, R. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.01.020 · Cited by 152 · see citing works
Nakazawa, S., Oikawa, D., Ishii, R., Ayaki, T., Takahashi, H., Takeda, H., Ishitani, R., Kamei, K., Takeyoshi, I., Kawakami, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms12547 · Cited by 151 · see citing works
Self-citationNeuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments
Jung, Y. J., Tweedie, D., Scerba, M. T., & Greig, N. H. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00313 · Cited by 154 · see citing works
Optineurin: A Coordinator of Membrane-Associated Cargo Trafficking and Autophagy
Ryan, T. A., & Tumbarello, D. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01024 · Cited by 131 · see citing works
Béland, L.-C., Markovinovic, A., Jakovac, H., De Marchi, F., Bilic, E., Mazzini, L., Kriz, J., & Munitic, I. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa124 · Cited by 125 · see citing works
Significance of optineurin mutations in glaucoma and other diseases
Minegishi, Y., Nakayama, M., Iejima, D., Kawase, K., & Iwata, T. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.08.002 · Cited by 123 · see citing works
Manghera, M., Ferguson-Parry, J., Lin, R., & Douville, R. N. (2016) · Journal of Virology · doi:10.1128/jvi.01503-16 · Cited by 118 · see citing works
Dysfunction of Optineurin in Amyotrophic Lateral Sclerosis and Glaucoma
Toth, R. P., & Atkin, J. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01017 · Cited by 114 · see citing works
Tadić, V., Prell, T., Lautenschläger, J., & Großkreutz, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00147 · Cited by 115 · see citing works
P53 Dysfunction in Neurodegenerative Diseases - The Cause or Effect of Pathological Changes?
Szybińska, A., & Leśniak, W. (2017) · Aging and Disease · doi:10.14336/ad.2016.1120 · Cited by 115 · see citing works
Cellular Functions of Optineurin in Health and Disease
Slowicka, K., Vereecke, L., & Loo, G. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.07.002 · Cited by 97 · see citing works
Sayyad, Z., Sirohi, K., Radha, V., & Swarup, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-17241-0 · Cited by 96 · see citing works
Markovinović, A., Cimbro, R., Ljutić, T., Križ, J., Rogelj, B., & Munitić, I. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.04.005 · Cited by 94 · see citing works
Su, X., Broach, J. R., Connor, J. R., Gerhard, G. S., & Simmons, Z. (2014) · Muscle & Nerve · doi:10.1002/mus.24198 · Cited by 93 · see citing works
Optineurin Insufficiency Impairs IRF3 but Not NF-κB Activation in Immune Cells
Munitić, I., Torchia, M. L. G., Meena, N. P., Zhu, G., Li, C. C., & Ashwell, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301696 · Cited by 85 · see citing works
Motor neuron disease and frontotemporal dementia: sometimes related, sometimes not
Hardy, J., & Rogaeva, E. A. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.11.006 · Cited by 80 · see citing works
Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin
Swarup, G., & Sayyad, Z. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01287 · Cited by 75 · see citing works
Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells
Picher-Martel, V., Dutta, K., Phaneuf, D., Sobue, G., & Julien, J.-P. (2015) · Molecular Brain · doi:10.1186/s13041-015-0162-6 · Cited by 65 · see citing works
NP001 regulation of macrophage activation markers in ALS: A phase I clinical and biomarker study
Miller, R. G., Zhang, R., Block, G. A., Katz, J., Barohn, R. J., Kasarskis, E. J., Forshew, D. A., Gopalakrishnan, V., & McGrath, M. S. (2014) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.3109/21678421.2014.951940 · Cited by 63 · see citing works
Tak, Y. J., Park, J.-H., Rhim, H., & Kang, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207525 · Cited by 62 · see citing works
The Links between ALS and NF-κB
Källstig, E., McCabe, B. D., & Schneider, B. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083875 · Cited by 59 · see citing works
Visual impairment in an optineurin mouse model of primary open-angle glaucoma
Tseng, H. C., Riday, T. T., McKee, C. A., Braine, C., Bomze, H. M., Barak, I., Marean‐Reardon, C. L., John, S. W. M., Philpot, B. D., & Ehlers, M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.02.012 · Cited by 59 · see citing works
Liu, Z., Li, H., Hong, C., Chen, M., Yue, T., Chen, C., Wang, Z., You, Q., Li, C., Weng, Q., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02647 · Cited by 58 · see citing works
Drug discovery and amyotrophic lateral sclerosis: Emerging challenges and therapeutic opportunities
Soares, P., Silva, C., Chavarria, D., Silva, F. S. G., Oliveira, P. J., & Borges, F. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101790 · Cited by 54 · see citing works
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Sirohi, K., & Swarup, G. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.08.020 · Cited by 50 · see citing works
Valionyte, E., Yang, Y., Roberts, S. L., Kelly, J., Lu, B., & Luo, S. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.11.012 · Cited by 50 · see citing works
The Regulatory Machinery of Neurodegeneration in In Vitro Models of Amyotrophic Lateral Sclerosis
Ikiz, B., Alvarez, M. J., Ré, D. B., Verche, V. L., Politi, K. A., Lotti, F., Phani, S., Pradhan, R., Yu, C., Croft, G. F., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.019 · Cited by 49 · see citing works
Zhang, C., Nie, P., Zhou, C., Hu, Y., Duan, S., Gu, M., Jiang, D., Wang, Y., Deng, Z., Chen, J., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03484-3 · Cited by 47 · see citing works
The role of autophagy in axonal degeneration of the optic nerve
Koch, J. C., & Lingor, P. (2016) · Experimental Eye Research · doi:10.1016/j.exer.2015.08.016 · Cited by 46 · see citing works
Mitophagy Modulation, a New Player in the Race against ALS
Madruga, E., Maestro, I., & Martı́nez, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020740 · Cited by 46 · see citing works
OPTN 691_692insAG is a founder mutation causing recessive ALS and increased risk in heterozygotes
Goldstein, O., Nayshool, O., Nefussy, B., Traynor, B. J., Renton, A. E., Gana‐Weisz, M., Drory, V. E., & Orr‐Urtreger, A. (2016) · Neurology · doi:10.1212/wnl.0000000000002334 · Cited by 43 · see citing works
Schiaffino, L., Bonafede, R., Scambi, I., Parrella, E., Pizzi, M., & Mariotti, R. (2018) · Scientific Reports · doi:10.1038/s41598-018-30659-4 · Cited by 42 · see citing works
Medchalmi, S., Tare, P., Sayyad, Z., & Swarup, G. (2021) · FEBS Journal · doi:10.1111/febs.15752 · Cited by 41 · see citing works
He, D., Xu, Y. C., Liu, M., & Cui, L. (2023) · Aging and Disease · doi:10.14336/ad.2023.0519 · Cited by 42 · see citing works
Phytochemistry and biosynthesis of δ-lactone withanolides
Yang, B., Xia, Y., Pan, J., Liu, Y., Wang, Q., & Kuang, H. (2015) · Phytochemistry Reviews · doi:10.1007/s11101-015-9420-6 · Cited by 40 · see citing works
METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma
Pan, Y., Suga, A., Kimura, I., Kimura, C., Minegishi, Y., Nakayama, M., Yoshitake, K., Iejima, D., Minematsu, N., Yamamoto, M., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci153589 · Cited by 39 · see citing works
Huang, Z., Liu, Q., Peng, Y., Dai, J., Xie, Y., Chen, W., Long, S., Pei, Z., Su, H., & Yao, X. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00218 · Cited by 38 · see citing works
Autophagy-related proteins: Potential diagnostic and prognostic biomarkers of aging-related diseases
Miceli, C., Leri, M., Stefani, M., & Bucciantini, M. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101967 · Cited by 39 · see citing works
Gene panels and primers for next generation sequencing studies on neurodegenerative disorders
Giau, V. V., An, S. S. A., Bagyinszky, E., & Kim, S. (2015) · Molecular & Cellular Toxicology · doi:10.1007/s13273-015-0011-9 · Cited by 37 · see citing works
Multiple Proteinopathies in Familial ALS Cases With Optineurin Mutations
Ayaki, T., Ito, H., Komure, O., Kamada, M., Nakamura, M., Wate, R., Kusaka, H., Yamaguchi, Y., Li, F., Kawakami, H., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx109 · Cited by 34 · see citing works
Self-citationFifita, J. A., Williams, K. L., Sundaramoorthy, V., McCann, E. P., Nicholson, G. A., Atkin, J. D., & Blair, I. P. (2016) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2016.1218517 · Cited by 34 · see citing works
Foster, A., Downing, P., Figredo, E., Polain, N., Stott, A., Layfield, R., & Rea, S. L. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103539 · Cited by 29 · see citing works
Effects of mutations and deletions in the human optineurin gene
Turturro, S. B., Shen, X., Shyam, R., Yue, B. Y., & Ying, H. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-99 · Cited by 28 · see citing works
Carata, E., Muci, M., Giulio, S. D., Mariano, S., & Panzarini, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411251 · Cited by 30 · see citing works
Loss of Optineurin In Vivo Results in Elevated Cell Death and Alters Axonal Trafficking Dynamics
Paulus, J. D., & Link, B. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109922 · Cited by 25 · see citing works
Functional analysis of optineurin and some of its disease-associated mutants
Bansal, M., Swarup, G., & Balasubramanian, D. (2015) · IUBMB Life · doi:10.1002/iub.1355 · Cited by 24 · see citing works
Tanishima, M., Takashima, S., Honda, A., Yasuda, D., Tanikawa, T., Ishii, S., & Maruyama, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.813899 · Cited by 24 · see citing works
Prospects for gene replacement therapies in amyotrophic lateral sclerosis
Giovannelli, I., Higginbottom, A., Kirby, J., Azzouz, M., & Shaw, P. J. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00751-5 · Cited by 23 · see citing works
Markovinović, A., Ljutić, T., Béland, L., & Munitić, I. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.07.007 · Cited by 23 · see citing works
Insights into the regulatory molecules involved in glaucoma pathogenesis
Moazzeni, H., Khani, M., & Elahi, E. (2020) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31833 · Cited by 23 · see citing works
Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients
Xie, Q., Li, K., Chen, Y., Li, Y., Jiang, W., Cao, W., Yu, H., Fan, D., & Deng, B. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00477-6 · Cited by 22 · see citing works
p53: from understanding its structure to advances in therapeutic targeting
Wang, W., Liu, X., Liu, H., Abolhassani, H., Yan, H., Zhang, H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02549-5 · Cited by 25 · see citing works
Yanagi, K. S., Wu, Z. J., Amaya, J., Chapkis, N., Duffy, A., Hajdarovic, K. H., Held, A., Mathur, A. D., Russo, K., Ryan, V. H., et al. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.10.033 · Cited by 21 · see citing works
Foster, A., Scott, D., Layfield, R., & Rea, S. L. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.04.001 · Cited by 19 · see citing works
You, Y., Park, S., Kwon, E., Kim, Y.-A., Hur, Y. M., Lee, G. I., Kim, S. M., Song, J. M., Kim, Y. J., Kim, Y. H., et al. (2024) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-31774-0 · Cited by 19 · see citing works
Tábuas‐Pereira, M., Santana, I. J., Kun‐Rodrigues, C., Brás, J., & Guerreiro, R. J. (2020) · Brain · doi:10.1093/brain/awaa183 · Cited by 17 · see citing works
The diverse role of optineurin in pathogenesis of disease
Guo, Q., Wang, J., & Weng, Q. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114157 · Cited by 17 · see citing works
Amyotrophic Lateral Sclerosis (ALS) prediction model derived from plasma and CSF biomarkers
Khosla, R., Rain, M., Sharma, S., & Anand, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247025 · Cited by 15 · see citing works
Effects of optineurin mutants on SH-SY5Y cell survival
Zhu, M. S., Li, A., Chen, J., Zhang, S., & Wu, J. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.03.003 · Cited by 15 · see citing works
Moazzeni, H., Mirrahimi, M., Moghadam, A., Banaei‐Esfahani, A., Yazdani, S., & Elahi, E. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz222 · Cited by 14 · see citing works
Identification of a splice variant of optineurin which is defective in autophagy and phosphorylation
Moharir, S. C., Bansal, M., Ramachandran, G., Ramaswamy, R., Rawat, S., Raychaudhuri, S., & Swarup, G. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.08.009 · Cited by 14 · see citing works
Optineurin regulates osteoblastogenesis through STAT1
Mizuno, N., Iwata, T., Ohsawa, R., Ouhara, K., Matsuda, S., Kajiya, M., Matsuda, Y., Kume, K., Tada, Y., Morino, H., et al. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.03.028 · Cited by 12 · see citing works
Self-citationKhosla, R., Rain, M., Chawathey, S., Modgil, S., Tyagi, R., Thakur, K., Pannu, V. S., Sharma, S., & Anand, A. (2020) · Muscle & Nerve · doi:10.1002/mus.27026 · Cited by 11 · see citing works
Optineurin associates with the podocyte Golgi complex to maintain its structure
Sippl, C., Zeilbeck, L. F., Fuchshofer, R., & Tamm, E. R. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1968-8 · Cited by 10 · see citing works
Moharir, S. C., Raghawan, A. K., Ramaswamy, R., & Swarup, G. (2022) · The Journal of Biochemistry · doi:10.1093/jb/mvac011 · Cited by 10 · see citing works
Yu, M., Ma, H., Lai, X., Wu, J., Shen, M., & Yan, J. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1592578 · Cited by 10 · see citing works
Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models
Chen, L., Zhang, S., Liu, S., & Gao, S. (2024) · Cells · doi:10.3390/cells13010099 · Cited by 8 · see citing works
Molecular aspects of cytoprotection by Optineurin during stress and disease
Swarup, G., Medchalmi, S., Ramachandran, G., & Sayyad, Z. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119895 · Cited by 5 · see citing works
Optineurin Dysfunction in Amyotrophic Lateral Sclerosis: Why So Puzzling?
Prtenjača, N. (2020) · Periodicum Biologorum · doi:10.18054/pb.v121-122i1-2.10627 · Cited by 5 · see citing works
Ishikawa, K.-I., Araki, M., Nagano, Y., Motoda, A., Shishido, T., Kurashige, T., Takahashi, T., Morino, H., Kawakami, H., Matsumoto, M., et al. (2021) · Differentiation · doi:10.1016/j.diff.2021.11.004 · Cited by 4 · see citing works
Self-citationSharma, S., Wahl, D., Risen, S. J., Gilberto, V. S., Chatterjee, A., Moreno, J. A., LaRocca, T. J., & Nagpal, P. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.07.583991 · Cited by 4 · see citing works
Age-related effects of optineurin deficiency in the mouse eye
Su, C., Liu, C., Adi, V., Chan, K. C., & Tseng, H. C. (2024) · Vision Research · doi:10.1016/j.visres.2024.108463 · Cited by 3 · see citing works
Medchalmi, S., Sayyad, Z., & Swarup, G. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2025.120064 · Cited by 1 · see citing works
Shi, X. C., Zhang, R. X., Feng, J. K., Chen, J. H., Zhang, J. F., Xiao, J. Y., Liu, X. P., Liu, H., Xia, B., Yao, L. N., et al. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003581 · Cited by 1 · see citing works
Optineurin regulates motor and learning behaviors by affecting dopaminergic neuron survival in mice
Yang, X., Zheng, R., Zhang, H., Ou, Z., Wan, S., Lin, D., Yan, J., Jin, M., & Tan, J. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115007 · Cited by 1 · see citing works
Lim, R., Barker, G., & Lappas, M. (2016) · Reproduction Fertility and Development · doi:10.1071/rd15494 · Cited by 1 · see citing works
Late-onset spinal motor neuronopathy- a new neuromuscular disease
Jokela, M. E. (2015) · UTUPub (University of Turku) · Cited by 1 · see citing works
Espina, Á. G. (2022) · Preprints.org · doi:10.20944/preprints202202.0013.v1
Sanford, Z. (2015) · Marshall Journal of Medicine · doi:10.18590/mjm.2015.vol1.iss1.3
Mammalian Expression and Biophysical Examination of Human Wild Type Optineurin Protein
Ying, H., Shen, X., Wang, M., & Yue, J. (2015)
[Non-autophagic degradation roles of autophagy receptors].
Wang, D., Zhang, B., Lü, B., & Wang, G. (2016) · PubMed
Gulcin, B., Çam, B. E., & Korkut, Ş. V. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.05.506596
An Understanding of Different Mechanisms Leading to Neurodegenerative Diseases
Sami, D. G., & Salama, M. (2023) · Springer eBooks · doi:10.1007/978-981-19-3949-5_10-1
Gene Therapy for Neurodegeneration in Glaucoma
Karl, J. J., & Tseng, H. C. (2024) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-99-4436-1_21
An Understanding of Different Mechanisms Leading to Neurodegenerative Diseases
Sami, D. G., & Salama, M. (2024) · Springer eBooks · doi:10.1007/978-981-99-7557-0_10
Godad, A. P., Vasant, T. L., Kurmi, S., & Borkar, M. R. (2026) · Springer eBooks · doi:10.1007/978-981-95-6099-8_5
Rôle de la protéine NEDL1, candidate dans la physiopathologie de la Sclérose Latérale Amyotrophique
Haouari, S. (2022) · theses.fr (ABES) · doi:10.70675/164dc935z4a7ez4257z84e0zdc1cb89f94c1
Cui, R., & Liu, X. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1824102
Ames, J. M., Kadam, R., Yadavalli, T., Patil, C. D., Bhattacharya, I., & Shukla, D. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag161
Dysfunctional mitophagy in Alzheimer's disease: evidence from peripheral optineurin
Patergnani, S., Trentini, A., Rosta, V., Guindani, P., Greatti, A., Pedrini, D., Meneguzzo, G., Rigon, L., Filippini, N., Giusto, E., et al. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.09.013
- Authors
- Akizuki, M., Yamashita, H., Uemura, K., Maruyama, H., Kawakami, H., Ito, H., & Takahashi, R.
- Affiliations
- Kyoto University (JP)
- Hiroshima University (JP)
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
- Corresponding author
- Yamashita, Hirofumi
- Ito, Hidefumi
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2013-06-17
- Volume
- 126
- Issue
- 6
- Pages
- 699-704
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1993813911
- Cited by
- 96
- References
- 23
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 10 · 2017: 6 · 2016: 9 · 2015: 11 · 2014: 7 · 2013: 2
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (24300132)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- optineurin, amyotrophic lateral sclerosis, NF-κB activation, neuronal cell death, loss-of-function mutations, withaferin A, mitochondrial apoptosis, p53, Bax, siRNA knockdown
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Antineoplastic Agents, Phytogenic, Cell Count, Cells, Cultured, Coloring Agents, Eye Proteins, Luciferases, Mutation, Neurons, Plasmids, Transfection, Trypan Blue, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Genes, p53, NF-kappa B, Cell Death, Genes, Reporter, Cell Cycle Proteins, Membrane Transport Proteins, RNA, Small Interfering, Mice, Withanolides, Real-Time Polymerase Chain Reaction
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