Amelioration of β-amyloid-induced cognitive dysfunction and hippocampal axon degeneration by curcumin is associated with suppression of CRMP-2 hyperphosphorylation
Abstract
The Alzheimer's disease (AD) brain is characterized by β-amyloid deposition, hyperphosphorylation of microtubule-associated proteins, formation of senile plaques and neurofibrillary tangles, and degeneration of specific neuronal populations. Collapsin response mediator protein 2 (CRMP-2) hyperphosphorylation has been implicated in AD-associated neural process regression and neurofibrillary tangle formation. Curcumin is a promising AD drug with incompletely defined therapeutic mechanisms. One possibility is that curcumin prevents β-amyloid-induced CRMP-2 hyperphosphorylation, thereby protecting against axonal regression and (or) promoting axonal regrowth. We examined spatial learning in the Morris water maze, hippocampal expression levels of CRMP-2 and phosphorylated CRMP-2 (p-CRMP-2) by Western blot, and NF-200 (an axon-specific marker) by immunohistochemistry in Sprague-Dawley rats subjected to a single intrahippocampal injection of Aβ1-40 alone or Aβ1-40 followed by curcumin (i.p. daily for 7 days). Compared to controls, spatial learning was significantly impaired in these Aβ1-40-injected AD model rats (P<0.05). In addition, hippocampal expression levels of CRMP-2 and NF-200 were reduced while p-CRMP-2 expression was significantly enhanced (P<0.05 for all). Overexpression of p-CRMP-2 was correlated with NF-200 underexpression (r(2)=-0.67308, P<0.05), suggesting that Aβ1-40 damaged hippocampal axons. Spatial learning deficits were reversed, CRMP-2 and NF-200 expression levels increased, and p-CRMP-2 expression reduced in curcumin-treated rats (all P<0.05). We propose that curcumin improves spatial learning by inhibiting CRMP-2 hyperphosphorylation, thus protecting against β-amyloid-induced hippocampal damage or promoting regeneration.
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Treatment with 300 mg/kg curcumin reversed spatial learning and memory impairment accompanied by hippocampal regeneration in the Aβ1-40 Alzheimer's disease model.
“The protective effect of curcumin on a Aβ1–40 AD model was documented by Wang et al. [132] and Yin et al. [133], where treatment with 300 mg/kg curcumin reversed spatial learning and memory impairment accompanied by hippocampal regeneration.”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [132]
Cites
1 retracted
RETRACTED ARTICLE: CRMP-2 Is Involved in Axon Growth Inhibition Induced by RGMa In Vitro and In Vivo
Wang, T., Wu, X., Yin, C., et al. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8385-3 · Cited by 30 · see citing works
RetractedThe Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m404751200 · Cited by 2,336 · see citing works
Jorm, A. F., & Jolley, D. (1998) · Neurology · doi:10.1212/wnl.51.3.728 · Cited by 886 · see citing works
Biological Properties of Curcumin-Cellular and Molecular Mechanisms of Action
Joe, B., Vijaykumar, M. H., & Lokesh, B. R. (2004) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408690490424702 · Cited by 815 · see citing works
CRMP-2 binds to tubulin heterodimers to promote microtubule assembly
Fukata, Y., Itoh, T. J., Kimura, T., Ménager, C., Nishimura, T., Shiromizu, T., Watanabe, H., Inagaki, N., Iwamatsu, A., Hotani, H., et al. (2002) · Nature Cell Biology · doi:10.1038/ncb825 · Cited by 761 · see citing works
The effect of curcumin (turmeric) on Alzheimer’s disease: An overview
Mishra, S., & Palanivelu, K. (2008) · Annals of Indian Academy of Neurology · doi:10.4103/0972-2327.40220 · Cited by 599 · see citing works
Neuroprotective effects of curcumin
Cole, G. M., Teter, B., & Frautschy, S. A. (2007) · ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY · doi:10.1007/978-0-387-46401-5_8 · Cited by 516 · see citing works
Thiyagarajan, M., & Sharma, S. S. (2003) · Life Sciences · doi:10.1016/j.lfs.2003.06.042 · Cited by 418 · see citing works
Nonsteroidal Anti-Inflammatory Drugs Can Lower Amyloidogenic Aß <sub>42</sub> by Inhibiting Rho
Zhou, Y., Su, Y., Li, B., Liu, F., Ryder, J. W., Wu, X., Gonzalez-DeWhitt, P. A., Gelfanova, V., Hale, J. E., May, P. C., et al. (2003) · Science · doi:10.1126/science.1090154 · Cited by 316 · see citing works
Phosphorylation by Rho Kinase Regulates CRMP-2 Activity in Growth Cones
Arimura, N., Ménager, C., Kawano, Y., Yoshimura, T., Kawabata, S., Hattori, A., Fukata, Y., Amano, M., Goshima, Y., Inagaki, M., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.22.9973-9984.2005 · Cited by 260 · see citing works
Gu, Y., Hamajima, N., & Ihara, Y. (2000) · Biochemistry · doi:10.1021/bi992323h · Cited by 176 · see citing works
Cole, A. R., Noble, W. J., van Aalten, L., Plattner, F., Meimaridou, R., Hogan, D., Taylor, M., LaFrancois, J. J., Gunn‐Moore, F. J., Verkhratsky, A., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04829.x · Cited by 166 · see citing works
Progressive brain dysfunction following intracerebroventricular infusion of beta1–42-amyloid peptide
Nakamura, S., Murayama, N., Noshita, T., Annoura, H., & Ohno, T. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02704-4 · Cited by 140 · see citing works
COLE, G. M., MORIHARA, T., LIM, G. P., YANG, F., BEGUM, A., & FRAUTSCHY, S. A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.005 · Cited by 129 · see citing works
Guo, L., Xing, Y., Pan, R., Jiang, M., Gong, Z., Lin, L., Wang, J., Xiong, G., & Dong, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070565 · Cited by 101 · see citing works
García‐Niño, W. R., Tapia, E., Zazueta, C., Zatarain-Barrón, Z. L., Hernández‐Pando, R., Vega-García, C. C., & Pedraza‐Chaverrí, J. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/424692 · Cited by 74 · see citing works
Williamson, R., van Aalten, L., Mann, D. M. A., Platt, B., Plattner, F., Bedford, L., Mayer, J., Howlett, D. R., Usardi, A., Sutherland, C. D., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110617 · Cited by 64 · see citing works
Chae, Y. C., Lee, S., Heo, K., et al. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.07.017 · Cited by 57 · see citing works
Veyrac, A., Giannetti, N., Charrier, E., Reymond, I., Aguera, M., Rogemond, V., Honnorat, J., & Jourdan, F. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04112.x · Cited by 44 · see citing works
Alteration of collapsin response mediator protein-2 expression in focal ischemic rat brain
Chung, M.-A., Lee, J., Lee, J.-Y., et al. (2005) · Neuroreport · doi:10.1097/01.wnr.0000176520.49841.e6 · Cited by 41 · see citing works
Lee, C.-Y., Jaw, T., Tseng, H., Chen, I., & Liou, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038789 · Cited by 40 · see citing works
Nazari, Q. A., Kume, T., Izuo, N., et al. (2013) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b13-00300 · Cited by 16 · see citing works
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Voulgaropoulou, S. D., van Amelsvoort, T. A. M. J., Prickaerts, J., & Vingerhoets, C. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146476 · Cited by 243 · see citing works
Mehla, J., Gupta, P., Pahuja, M., Diwan, D., & Diksha, D. (2020) · Brain Sciences · doi:10.3390/brainsci10120964 · Cited by 108 · see citing works
- Authors
- Wang, Y., Yin, H., Li, J., Zhang, Y., Han, B., Zeng, Z., Qiao, N., Cui, X., Lou, J., & Li, J.
- Affiliations
- Second Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Wang, Yunliang
- Lou, Jiyu
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 557
- Pages
- 112-117
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2066345981
- Cited by
- 36
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 3
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30770762)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- curcumin, amyloid-beta, CRMP2, Alzheimer's disease, axon regeneration, spatial learning, cognitive impairment, neurofilament 200, intrahippocampal injection, neuroprotection
- MeSH terms
- Animals, Axons, Curcumin, Hippocampus, Immunohistochemistry, Male, Nerve Degeneration, Nerve Tissue Proteins, Phosphorylation, Blotting, Western, Amyloid beta-Peptides, Rats, Sprague-Dawley, Neuroprotective Agents, Maze Learning, Intercellular Signaling Peptides and Proteins, Rats
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