Leptin Signaling Plays a Critical Role in the Geniposide-Induced Decrease of Tau Phosphorylation
Abstract
We have previously demonstrated that geniposide attenuates the production of Aβ1-42 both in vitro and in vivo via enhancing leptin receptor signaling. But the role played by geniposide in the phosphorylation of tau and its underlying molecular mechanisms remain unclear. In this study, we investigated the effect of geniposide on the phosphorylation of tau and the role of leptin signaling in this process. Our data suggested that, accompanied by the up-regulation of leptin receptor expression, geniposide significantly decreased the phosphorylation of tau in rat primary cultured cortical neurons and in APP/PS1 transgenic mice, and this geniposide-induced decrease of tau phosphorylation could be prevented by leptin antagonist (LA). Furthermore, LA also prevented the phosphorylation of Akt at Ser-473 site and GSK-3β at Ser-9 site induced by geniposide. All these results indicate that geniposide may regulate tau phosphorylation through leptin signaling, and geniposide may be a promising therapeutic compound for the treatment of Alzheimer's disease in the future.
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In APP/PS1 mice, geniposide's inhibitory effect on Tau hyperphosphorylation and Aβ1-42 production is due to increased leptin signaling.
“Other studies performed in APP/PS1 have suggested that the inhibitory effect of geniposide on Tau hyperphosphorylation and Aβ1-42 production is due to an increase of leptin signaling (Liu et al., 2015; Liu et al., 2017)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Liu et al., 2015
Cites
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987 · see citing works
Glycogen synthase kinase‐3 and the Alzheimer‐like state of microtubule‐associated protein tau
Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J., Vandenheede, J. R., & Mandelkow, E. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)81496-9 · Cited by 515 · see citing works
GSK-3β, a pivotal kinase in Alzheimer disease
Llorens-MarÃtin, M., Jurado, J., Hernández, F., & Ãvila, J. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00046 · Cited by 451 · see citing works
GSK-3 is essential in the pathogenesis of Alzheimer's disease
Takashima, A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s335 · Cited by 395 · see citing works
Wagner, U., Utton, M. A., Gallo, J., & Miller, C. C. J. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.6.1537 · Cited by 255 · see citing works
Leptin Reduces Pathology and Improves Memory in a Transgenic Mouse Model of Alzheimer's Disease
Greco, S. J., Bryan, K. J., Sarkar, S., Zhu, X., Smith, M. A., Ashford, J. W., Johnston, J. M., Tezapsidis, N., & Casadesús, G. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1308 · Cited by 218 · see citing works
Tau phosphorylation by GSK-3β promotes tangle-like filament morphology
Rankin, C. A., Sun, Q., & Gamblin, T. C. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-12 · Cited by 214 · see citing works
Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells
Greco, S. J., Sarkar, S., Johnston, J. M., & Tezapsidis, N. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.041 · Cited by 191 · see citing works
Liu, J., Yin, F., Zheng, X., Jing, J., & Hu, Y. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.04.021 · Cited by 145 · see citing works
Self-citationGao, C., Liu, Y., Jiang, Y., Ding, J., & Li, L. (2013) · Brain Pathology · doi:10.1111/bpa.12116 · Cited by 141 · see citing works
Liu, J., Yin, F., Guo, L., Deng, X., & Hu, Y. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2008.25 · Cited by 140 · see citing works
Leptin: A Novel Therapeutic Strategy for Alzheimer's Disease
Tezapsidis, N., Johnston, J. M., Smith, M. A., Ashford, J. W., Casadesús, G., Robakis, N. K. R. K., Wolozin, B. L., Perry, G. L., Zhu, X., Greco, S. J., et al. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1021 · Cited by 124 · see citing works
Leptin inhibits glycogen synthase kinase-3β to prevent tau phosphorylation in neuronal cells
Greco, S. J., Sarkar, S., Casadesús, G., Zhu, X., Smith, M. A., Ashford, J. W., Johnston, J. M., & Tezapsidis, N. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.03.066 · Cited by 119 · see citing works
Greco, S. J., Hamzelou, A., Johnston, J. M., Smith, M. A., Ashford, J. W., & Tezapsidis, N. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.09.050 · Cited by 88 · see citing works
Neurotrophic Property of Geniposide for Inducing the Neuronal Differentiation of PC12 Cells
Liu, J., Zheng, X., Yin, F., Hu, Y., Guo, L., Deng, X., Chen, G., Jiajia, J., & Zhang, H. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2006.08.009 · Cited by 86 · see citing works
Self-citationLi, X.-C., Lu, F., Tian, Q., Yang, Y., Wang, Q., & Wang, J.-H. (2005) · Journal of neural transmission · doi:10.1007/s00702-005-0303-7 · Cited by 70 · see citing works
Zhang, Y., Yin, F., Liu, J., Liu, Z., Guo, L., Xia, Z., & Zidichouski, J. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.04.002 · Cited by 45 · see citing works
Negishi, T., Ishii, Y., Kyuwa, S., Kuroda, Y., & Yoshikawa, Y. (2003) · Neuroscience Letters · doi:10.1016/j.neulet.2003.09.031 · Cited by 42 · see citing works
Geniposide decreases the level of Aβ1−42 in the hippocampus of streptozotocin-induced diabetic rats
Liu, J., Zhang, Y., Deng, X., & Yin, F. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmt069 · Cited by 32 · see citing works
Yin, F., Zhang, Y., Guo, L., Kong, S., & Liu, J. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311211080015 · Cited by 28 · see citing works
Leptin: The Missing Link in Alzheimer Disease?
Harvey, J. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2010.144006 · Cited by 26 · see citing works
Xu, G., Deng, Y.-Q., Liu, S.-J., Li, H.-L., & Wang, J. (2005) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2005.00050.x · Cited by 19 · see citing works
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Tian, J., Qin, S., Han, J., Meng, J., & Liang, A. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.114984 · Cited by 111 · see citing works
Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide
Zhou, Y., Zhang, R., Rahman, K., Cao, Z., Zhang, H., & Peng, C. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/4925682 · Cited by 97 · see citing works
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Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
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Habtemariam, S. (2018) · Molecules · doi:10.3390/molecules23010117 · Cited by 55 · see citing works
Wojtunik‐Kulesza, K. A., Rudkowska, M., Kasprzak‐Drozd, K., Oniszczuk, A., & Borowicz, K. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147366 · Cited by 50 · see citing works
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Zhang, W., Zhang, F., Hu, Q., Xiao, X., Ou, L., Chen, Y., Luo, S., Cheng, Y., Jiang, Y., Ma, X., et al. (2021) · Chinese Medicine · doi:10.1186/s13020-021-00486-3 · Cited by 46 · see citing works
Lilamand, M., Bouaziz-Amar, E., Dumurgier, J., Cognat, E., Hourregue, C., Mouton-Liger, F., Sanchez, M., Troussière, A.-C., Martinet, M., Hugon, J., et al. (2023) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glac234 · Cited by 27 · see citing works
Campolim, C. M., Schimenes, B. C., Veras, M. M., Kim, Y., & Prada, P. O. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1401800 · Cited by 19 · see citing works
Ablinger, I., Dressel, K., Rott, T., Lauer, A. A., Tiemann, M., Batista, J. P., Taddey, T., Grimm, H. S., & Grimm, M. O. W. (2022) · Biomedicines · doi:10.3390/biomedicines10112922 · Cited by 5 · see citing works
- Authors
- Liu, J., Liu, Z., Zhang, Y., & Yin, F.
- Affiliations
- Chongqing Technology and Business University (CN)
- Chongqing University of Technology (CN)
- Venue
- Acta Biochimica et Biophysica Sinica
- Published
- 2015-12-01
- Volume
- 47
- Issue
- 12
- Pages
- 1018-1022
- ISSN
- 1672-9145 (ISSN-L)
- OpenAlex
- W2300360012
- Cited by
- 11
- References
- 23
- Citations by year
- 2024: 2 · 2022: 4 · 2021: 3 · 2019: 1 · 2018: 1
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biochimica et Biophysica Sinica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81173063)
- Chongqing Science Found for Distinguished Young Scholars from Chongqing Science & Technology Community (2014jcyjjq10003)
- Innovation of Science and Technology Leading Talent in Chongqing from Chongqing Science & Technology Community (2014kjcxljrc0009)
- Chongqing Natural Science Foundation
- Chongqing Science & Technology Community (2013jjb10032)
- Innovative Research Team Development Program in University of Chongqing (KJTD 201314)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- geniposide, leptin signaling, leptin receptor, tau phosphorylation, Alzheimer's disease, APP/PS1 mice, cortical neurons, Akt phosphorylation, GSK3β phosphorylation, leptin antagonist, amyloid-beta 42
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Phosphorylation, Signal Transduction, tau Proteins, Leptin, Iridoids, Mice, Rats, Receptors, Leptin
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