Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway
Open accessAbstract
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.
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Osmotin has neuroprotective effects by preventing memory impairment and neuroinflammation induced by amyloid or LPS injections.
“Other studies have demonstrated its neuroprotective effects by preventing memory impairment and neuroinflammation induced by either amyloid or LPS injections [128,129].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [129]
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Cites
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304 · see citing works
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
The Nuclear Factor NF- B Pathway in InflammationPreprint
Lawrence, T. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001651 · Cited by 4,926 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
Adiponectin and Adiponectin Receptors
Kadowaki, T., & Yamauchi, T. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0005 · Cited by 2,634 · see citing works
Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J., Knapp, D. J., & Crews, F. T. (2007) · Glia · doi:10.1002/glia.20467 · Cited by 2,144 · see citing works
Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10689 · Cited by 1,924 · see citing works
Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway
Tournier, C., Hess, P., Yang, D. D., Xu, J., Turner, T. K., Nimnual, A., Bar-Sagi, D., Jones, S. N., Flavell, R. A., & Davis, R. J. (2000) · Science · doi:10.1126/science.288.5467.870 · Cited by 1,728 · see citing works
Recognition of lipopolysaccharide pattern by TLR4 complexes
Park, B. S., & Lee, J. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.97 · Cited by 1,244 · see citing works
Lehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052 · see citing works
CD14 Controls the LPS-Induced Endocytosis of Toll-like Receptor 4
Zanoni, I., Ostuni, R., Marek, L. R., Barresi, S., Barbalat, R., Barton, G. M., Granucci, F., & Kagan, J. C. (2011) · Cell · doi:10.1016/j.cell.2011.09.051 · Cited by 997 · see citing works
Positive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation
Delhase, M., Hayakawa, M., Chen, Y., & Karin, M. (1999) · Science · doi:10.1126/science.284.5412.309 · Cited by 852 · see citing works
Griffin, W. S. T., Sheng, J. G., Royston, M. C., Gentleman, S., McKenzie, J. E., Graham, D. I., Roberts, G. W., & Mrak, R. E. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00136.x · Cited by 708 · see citing works
Innate immunity: the missing link in neuroprotection and neurodegeneration?
Nguyen, M. D., Julien, J., & Rivest, S. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn752 · Cited by 698 · see citing works
CD14 and Toll-Like Receptors 2 and 4 Are Required for Fibrillar Aβ-Stimulated Microglial Activation
Reed-Geaghan, E. G., Savage, J. C., Hise, A. G., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3158-09.2009 · Cited by 591 · see citing works
Inflammatory Neurodegeneration and Mechanisms of Microglial Killing of Neurons
Brown, G. C., & Neher, J. J. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8105-9 · Cited by 526 · see citing works
JNK-Mediated BIM Phosphorylation Potentiates BAX-Dependent Apoptosis
Putcha, G. V., Le, S., Frank, S., Besirli, C. G., Clark, K., Chu, B., Alix, S., Youle, R. J., LaMarche, A., Maroney, A. C., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00355-6 · Cited by 518 · see citing works
Toll-like receptor signaling in neural plasticity and disease
Okun, E., Griffioen, K. J. S., & Mattson, M. P. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.02.005 · Cited by 513 · see citing works
Microglia Biology in Health and Disease
Garden, G. A., & Möller, T. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9015-5 · Cited by 494 · see citing works
Role of toll-like receptor signalling in A uptake and clearance
Tahara, K., Kim, H.-D., Jin, J.-J., Maxwell, J. A., Li, L., & Fukuchi, K.-I. (2006) · Brain · doi:10.1093/brain/awl249 · Cited by 493 · see citing works
Inflammatory processes in Alzheimer's disease
McGeer, E. G., & McGeer, P. L. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00124-6 · Cited by 473 · see citing works
Gorina, R., Font-Nieves, M., Márquez‐Kisinousky, L., Santalucı́a, T., & Planas, A. M. (2010) · Glia · doi:10.1002/glia.21094 · Cited by 470 · see citing works
Sastre, M., Dewachter, I., Landreth, G. E., Willson, T. M., Klockgether, T., LEUVEN, F. V., & Heneka, M. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09796.2003 · Cited by 359 · see citing works
LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-α
Xaus, J., Comalada, M., Valledor, A. F., Lloberas, J., López-Soriano, F., Argilés, J. M., Bogdan, C., & Celada, A. (2000) · Blood · doi:10.1182/blood.v95.12.3823 · Cited by 331 · see citing works
Adiponectin in health and disease
Oh, D. K., Ciaraldi, T. P., & Henry, R. R. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00610.x · Cited by 289 · see citing works
ACRP30, a new hormone controlling fat and glucose metabolism
Tsao, T., Lodish, H. F., & Fruebis, J. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01430-9 · Cited by 278 · see citing works
Narasimhan, M. L., Coca, M. A., Jin, J., Yamauchi, T., Ito, Y., Kadowaki, T., Kim, K. K., Pardo, J. M., Damsz, B., Hasegawa, P. M., et al. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.11.050 · Cited by 216 · see citing works
Font-Nieves, M., Sans-Fons, M. G., Gorina, R., Bonfill‐Teixidor, E., Salas-Perdomo, A., Márquez‐Kisinousky, L., Santalucı́a, T., & Planas, A. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.327874 · Cited by 204 · see citing works
Lee, Y., Choi, D., Yun, Y., Han, S., Oh, K., & Hong, J. T. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.06.011 · Cited by 195 · see citing works
Gene structure and organization of the human β‐secretase ( BACE ) promoter
Sambamurti, K., Kinsey, R., Maloney, B., Ge, Y., & Lahiri, D. K. (2004) · The FASEB Journal · doi:10.1096/fj.03-1378fje · Cited by 179 · see citing works
Parajuli, B., Sonobe, Y., Kawanokuchi, J., Doi, Y., Noda, M., Takeuchi, H., Mizuno, T., & Suzumura, A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-268 · Cited by 159 · see citing works
Rosi, S., Vazdarjanova, A. I., Ramı́rez-Amaya, V., Worley, P. F., Barnes, C. A., & Wenk, G. L. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.017 · Cited by 158 · see citing works
Hwang, D. Y., Chae, K. R., Kang, T. S., Hwang, J. H., Lim, C. H., Kang, H. K., Goo, J. S., Lee, M. R., Lim, H. J., Min, S. H., et al. (2002) · The FASEB Journal · doi:10.1096/fj.01-0732com · Cited by 147 · see citing works
Ali, T., Yoon, G. H., Shah, S. A., Lee, H. Y., & Kim, M. O. (2015) · Scientific Reports · doi:10.1038/srep11708 · Cited by 146 · see citing works
Chan, K., Lam, K. S. L., Cheng, O.-Y., Kwan, J., Ho, P. W., Cheng, K. K. Y., Chung, S. K., Ho, J. W.-M., Guo, V. Y., & Xu, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052354 · Cited by 140 · see citing works
Teeling, J. L., Cunningham, C., Newman, T. A., & Perry, V. H. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.11.006 · Cited by 139 · see citing works
Badshah, H., Ali, T., Rehman, S. U., Amin, F.-U., Ullah, F., Kim, T. H., & Kim, M. O. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9623-z · Cited by 125 · see citing works
Self-citationGárate, I., García‐Bueno, B., Madrigal, J. L. M., Caso, J. R., Alou, L., Gómez-Lus, M. L., & Leza, J. C. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-8 · Cited by 125 · see citing works
Praticò, D., & Trojanowski, J. Q. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00141-x · Cited by 116 · see citing works
Munshi, N., Fernandis, A. Z., Cherla, R. P., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5860 · Cited by 110 · see citing works
Synaptic Dysfunction in Alzheimer’s Disease
Marcello, E. E., Epis, R., Saraceno, C., & Luca, M. D. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-3-7091-0932-8_25 · Cited by 107 · see citing works
Rupinder, S. K., Aulakh, G. K., & Singh, M. (2007) · Vascular Pharmacology · doi:10.1016/j.vph.2007.01.006 · Cited by 91 · see citing works
Dong, M., Hu, N., Hua, Y., Xu, X., Kandadi, M. R., Guo, R., Jiang, S., Nair, S., Hu, D., & Ren, J. T. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.02.023 · Cited by 86 · see citing works
Deng, X., Li, M., Ai, W., He, L., Lu, D., Patrylo, P. R., Cai, H., Luo, X., Li, Z., & Yan, X. (2014) · Advances in Alzheimer s Disease · doi:10.4236/aad.2014.32009 · Cited by 75 · see citing works
Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury
Jenke, A., Wilk, S., Poller, W. C., Eriksson, U., Valaperti, A., Rauch, B. H., Stroux, A., Liu, P. J., Schultheiß, H., Scheibenbogen, C., et al. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt118 · Cited by 72 · see citing works
Cederbaum, A. I., Yang, L., Wang, X., & Wu, D. (2011) · International Journal of Hepatology · doi:10.1155/2012/582790 · Cited by 67 · see citing works
Insights Into Sepsis Therapeutic Design Based on the Apoptotic Death Pathway
Hattori, Y., Takano, K., Teramae, H., Yamamoto, S., Yokoo, H., & Matsuda, N. (2010) · Journal of Pharmacological Sciences · doi:10.1254/jphs.10r04cr · Cited by 60 · see citing works
Poly-ADP-ribosylation in health and disease
Koh, D. W., Dawson, T. M., & Dawson, V. L. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4508-y · Cited by 59 · see citing works
Naseer, M. I., Ullah, I., Narasimhan, M. L., Lee, H. Y., Bressan, R. A., Yoon, G. H., Yun, D., & Kim, M. O. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.53 · Cited by 58 · see citing works
Self-citationToll-like receptor signaling in sepsis
Lakhani, S., & Bogue, C. (2003) · Current opinion in pediatrics · doi:10.1097/00008480-200306000-00009 · Cited by 55 · see citing works
Miele, M., Costantini, S., & Colonna, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016690 · Cited by 51 · see citing works
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- Sambamurti K. et al. Gene structure and organization of the human beta-secretase (BACE) promoter. FASEB J. 18, 1034– 6 (2004). 15059975
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Ahmad, A., Ali, T., Kim, M. W., Khan, A., Jo, M. H., Rehman, S. U., Khan, M. S., Abid, N. B., Khan, M., Ullah, R., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2018.10.004 · Cited by 76 · see citing works
Abou-Samra, M., Selvais, C. M., Dubuisson, N., & Brichard, S. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072620 · Cited by 72 · see citing works
Liu, Y., Vu, V., & Sweeney, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00842 · Cited by 69 · see citing works
Ali, T., Rehman, S. U., Khan, A., Badshah, H., Abid, N. B., Kim, M. W., Jo, M. H., Chung, S. S., Lee, H.-G., Rutten, B. P. F., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00445-4 · Cited by 65 · see citing works
Self-citationTakahashi, Y., Watanabe, R., Sato, Y., Ozawa, N., Kojima, M., Watanabe-Kominato, K., Shirai, R., Sato, K., Hirano, T., & Watanabe, T. (2018) · Metabolism · doi:10.1016/j.metabol.2018.01.010 · Cited by 40 · see citing works
Liu, J., Sui, H., Zhao, J., & Wang, Y. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00611 · Cited by 38 · see citing works
- Authors
- Badshah, H., Ali, T., & Kim, M. O.
- Affiliations
- Gyeongsang National University (KR)
- Corresponding author
- Kim, Myeong Ok
- Venue
- Scientific Reports
- Published
- 2016-04-20
- Volume
- 6
- Issue
- 1
- Pages
- 24493-24493
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4837357
- OpenAlex
- W2338113233
- Cited by
- 217
- References
- 52
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 23 · 2023: 14 · 2022: 32 · 2021: 21 · 2020: 38 · 2019: 20 · 2018: 23 · 2017: 18 · 2016: 4
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea (2012-0009521)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- osmotin, neuroinflammation, memory impairment, TLR4 signaling, NF-κB signaling, lipopolysaccharide, AdipoR1, Alzheimer's disease, microglia, synaptic function, neurodegeneration, apoptosis, plant defense peptides, neuroprotection
- MeSH terms
- Animals, Astrocytes, Cell Line, Disease Models, Animal, Hippocampus, Inflammation, Lipopolysaccharides, Male, Memory Disorders, Synaptic Transmission, Plant Growth Regulators, Signal Transduction, Biomarkers, NF-kappa B, Apoptosis, Microglia, Maze Learning, Neurodegenerative Diseases, Toll-Like Receptor 4, Mice
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