Since it has been shown that Alzheimer’s disease is accompanied by higher peripheral concentrations of cytokines, we focused on the correction of chronic inflammation causing Aβ excess and aggregation what should have a positive impact. Proinflammatory cytokines action is realized by NF-κB intracellular signals. Curcumin can inhibit activation of the proinflammatory transcription factor NF-κB and is able to be mounted in the amyloid-β fibrils and encourage their disaggregation. To study the influence of anti-inflammatory effect of curcumin and its ability to model complexes with a fragment of AβPP. Investigation was carried out on rats with model of Alzheimer’s disease using nasal therapy with curcumin Concentration of cytokines in cerebral cortex, hippocampus and blood serum, and indicators of conditioned active escape reflex were determined in this study. Methods of molecular dynamics and docking were used to examine the interactions of curcumin with fragment of AβPP. Аβ42_Human in the hippocampus of rats provoked chronic neuroinflammation specifically and primarily at the injection site. Curcumin performance revealed specific depressing effect on cytokines in the cerebral cortex and in the hippocampus it appeared similar to the above, but of lower level. Anti-inflammatory activity of curcumin led to the recovery of memory parameters. Analysis of restriction sites of AβPP has shown that position of curcumin in Site II is energetically more favorable for binding. Our suggestion that curcumin is an effective anti-cytokine factor was confirmed by experimental results obtained in vivo and explain the mechanism describing its effect on NF-κB Curcumin doesn’t block the excision Aβ but binding with its hydrophobic region.
| Published in | Advances in Biochemistry (Volume 4, Issue 4) |
| DOI | 10.11648/j.ab.20160404.11 |
| Page(s) | 34-46 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2016. Published by Science Publishing Group |
Alzheimer's Disease, Curcumin, Amyloid-β, Cytokine, Rat, Docking
| [1] | Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J Amyloid-Beta: A Crucial Factor in Alzheimer’s Disease. Med Princ Pract. 2015; 42: 1-10. |
| [2] | Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol. 2013; 73: 104-119. |
| [3] | Palop JJ, Mucke L Amyloid-β-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat Neurosci. 2010; 13: 812-818. |
| [4] | Hardy J, Selkoe DJ The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297: 353-356. |
| [5] | Grienberger C, Rochefort NL, Adelsberger H, Henning HA, Hill DN, Reichwald J, Staufenbiel M, Konnerth A Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease. Nat Commun. 2012; 774: 1-10. |
| [6] | Nakajima C, Kulik A, Frotscher M, Herz J, Schäfer M, Bock HH, May P LDL receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes. J Biol Chem. 2013; 30: 21909-21923. |
| [7] | Selkoe DJ Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior. Behav Brain Res. 2008; 192: 106-113. |
| [8] | O'Brien RJ, Wong PC Amyloid precursor protein processing and Alzheimer's disease. Annu Rev Neurosci. 2011; 34: 185-204. |
| [9] | Maltsev AV, Dovidchenko NV, Uteshev VK, Sokolik VV, Shtang OM, Yakushin MA, Sokolova NM, Surin AK, Galzitskaya OV Intensive pro-tein synthesis in neurons and phosphorylation of beta-amyloid precursor pro-tein and tau-protein are triggering factors of neuronal amyloidosis and Alz-heimer’s disease. Biomed Chem. 2013; 7: 278-293. |
| [10] | Kim J-H, Anwyl R, Suh Y-H, Djamgoz MBA, Rowan MJ Use-dependent effects of amyloidogenic fragments of β-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo. J Neurosci. 2001; 21: 1327-1333. |
| [11] | Hartmann T, Bieger SC Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides. Nat Med. 1997; 3: 1016-1020. |
| [12] | Colombo A, Bastone A, Ploia C, Sclip A, Salmona M, Forloni G, Borsello T JNK regulates APP cleavage and degradation in a model of Alzheimer's disease. Neurobiol Dis. 2009; 33: 518-525. |
| [13] | Andersen OM, Reiche J, Schmidt V Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci USA. 2005; 102: 13461-13466. |
| [14] | Ridge PG, Ebbert MT, Kauwe JS Genetics of Alzheimer's disease. Biomed Res Int. 2013; 25: 49-54. |
| [15] | Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science. 1996; 274: 99-102. |
| [16] | Fantini J, Garmy N, Mahfoud R Lipid rafts: structure, function and role in HIV, Alzheimer’s and prion diseases. Expert Rev Mol Med. 2002; 4: 1-22. |
| [17] | Puzzo D, Privitera L, Fa’ M Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory. Ann Neurol. 2011; 69: 819-830. |
| [18] | Kimura R, MacTavish D, Yang J, Westaway D, Jhamandas JH Beta amyloid-induced depression of hippocampal long-term potentiation is mediat-ed through the amylin receptor. J Neurosci. 2012; 32: 17401-17406. |
| [19] | Morley JE, Farr SA A physiological role for amyloid-β protein: en-hancement of learning and memory. J Alzheimer’s disease. 2010; 19: 441-449. |
| [20] | Cárdenas-Aguayo MC, Silva-Lucero MC Physiological role of amyloid beta in neural cells: the cellular trophic activity. INTECH. 2014: 1-26. |
| [21] | Cirrito JR, May PC, O’Dell MA In vivo assessment of brain intersti-tial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci. 2003; 23: 8844-8853. |
| [22] | Puzzo D, Privitera L Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008; 28: 14537-14545. |
| [23] | Atwood CS, Obrenovich ME, Liu T, Chan H Amyloid-beta: a chame-leon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta. Brain Res Brain Res Rev. 2003; 43: 1-16. |
| [24] | Cetin F, Yazihan N, Dincer S, Akbulut G The effect of intrahippocampal beta-amyloid1-42 peptide injection on oxidant and antioxidant status in rat brain. Ann NY Acad Sci. 2007; 1100: 510-517. |
| [25] | Curtain CC, Ali F, Volitakis I Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. J Biol Chem. 2001; 276: 20466-20473. |
| [26] | Chen Y, Dong C Abeta40 promotes neuronal cell fate in neural pro-genitor cells. Cell Death Differ. 2009; 16: 386-394. |
| [27] | Atwood CS, Bishop GM, Perry G, Smith MA Amyloid-beta: a vas-cular sealant that protects against hemorrhage? J Neurosci Res. 2002; 70: 356. |
| [28] | Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hy-man B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD The Alz-heimer’s disease-associated amyloid β-protein is an antimicrobial peptide. PLoS ONE. 2010; 5 (3): e9505. |
| [29] | Gu Z, Zhong P, Yan Z Activation of muscarinic receptors inhibits be-ta-amyloid peptide-induced signaling in cortical slices. J Biol Chem. 2003; 278: 17546-17556. |
| [30] | Jellinger KA Challenges in neuronal apoptosis. Curr Alzheimer Res. 2006; 3: 377-391. |
| [31] | Goure WF, Krafft GA, Jerecic J, Hefti F Targeting the proper amy-loid-beta neuronal toxins: a path forward for Alzheimer's disease immunother-apeutics. Alzheimers Res Ther. 2015; 6: 42. |
| [32] | Sakono M, Zako T Amyloid oligomers: formation and toxicity of Aβ oligomers. FEBS J. 2010; 277: 1348-1358. |
| [33] | Moreth J, Kroker KS, Schwanzar D, Schnack C Globular and proto-fibrillar Aβ aggregate simper neurotransmission by different mechanism. Bio-chem. 2013; 52: 1466-1476. |
| [34] | Tamburri A, Dudilot A, Licea S, Bourgeois C, Boehm J NMDA-receptor activation but not ion flux is required for amyloid-beta induced syn-aptic depression. PLoS One. 2013; 8: e65350. |
| [35] | Takamura A, Sato Y, Watabe D, Okamoto Y Sortilin is required for toxicaction of Aβ oligomers (AβOs): extracellular AβOs trigger apoptosis, and intraneuronal AβOs impair degradation pathways. Life Sci. 2012; 91: 1177-1186. |
| [36] | Slack BE, Wurtman RJ Regulation of synthesis and metabolism of the amyloid precursor protein by extracellular signals. In: Research progress in Alzheimer's disease and dementia. M.-K. Sun, ed. 2007; 2: 1-25, Nova Science Publishers, Inc. |
| [37] | Mattson MP Pathways towards and away from Alzheimer's disease. Nature. 2004; 430: 631-639. |
| [38] | Inflammatory diseases - immunopathology, clinical and pharmaco-logical bases; in Khatami M (ed): Mehan S, Arora R, Sehgal V, Sharma D, Sharma G Dementia: A Complete Literature Review on Various Mechanisms Involved in Pathogenesis and an Intracerebroventricular Streptozotocin-Induced Alzheimer's Disease. Rijeka, InTech. 2012: 3-19. |
| [39] | Swardfager W, Lanctôt K, Rothenburg L A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry. 2010; 68: 930-941. |
| [40] | Minati L, Edginton T, Bruzzone MG, Giaccone G Current concepts in Alzheimer’s disease: a multidisciplinary review. Am J Alzheim Dis & Other Dementia. 2009; 24: 95-121. |
| [41] | Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J Therapeutic approaches to Alzheimer’s disease. Brain. 2006; 129: 2840-2855. |
| [42] | Necula M, Kayed R, Milton S, Glabe CG Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. J Biol Chem. 2007; 282: 10311-10324. |
| [43] | Birks J Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006: CD005593. |
| [44] | Gotti C, Riganti L, Vailati S, Clementi F Brain neuronal nicotinic receptors as new targets for drug discovery. Curr Pharm Des. 2006; 12: 407-428. |
| [45] | Palmer GC Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies. Curr Drug Targets. 2001; 2: 241-271. |
| [46] | Ostrowski SM, Wilkinson BL, Golde TE, Landreth G. Statins reduce amyloid-beta production through inhibition of protein isoprenylation. J Biol Chem. 2007; 282: 26832-26844. |
| [47] | Gray SL, Anderson ML, Crane PK, Breitner JC Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. J Am Geriatr Soc. 2008; 56: 291-295. |
| [48] | Dinarello CA Proinflammatory cytokines. Chest. 2000; 118: 503-508. |
| [49] | Hunter CA, Timans J, Pisacane P Comparison of the effects of inter-leukin-1, interleukin-1 and interferon- inducing factor on the production of interferon- by natural killer. Eur J Immunol. 1997; 27: 2787-2792. |
| [50] | Engelmann H, Novick D Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem. 1990; 265: 1531-1536. |
| [51] | Dinarello CA Anti-cytokine therapies in response to systemic infection. J Investigative Dermatology Symposium Proceedings. 2001; 6: 244-250. |
| [52] | Huber TS, Gaines GS, Welborn MB Anticytokine therapies for acute inflammation and the systemic inflammatory response syndrome: IL-10 and ischemia/reperfusion injury as a new paradigm. Shock. 2000; 13: 425-434. |
| [53] | Lee WH, Loo CY, Bedawy M, Luk F, Mason RS, Rohanizadeh R Curcumin and its derivatives: their application in neuropharmacology and neu-roscience in the 21st century. Curr Neuropharmacol. 2013; 11: 338-378. |
| [54] | Shezad A, Lee YS (2013) Molecular mechanisms of curcumin action: signal transduction. Biofactors. 2013; 39: 27-36. |
| [55] | Aggarwal BB, Kumar A, Bharti AC Anticancer potential of curcu-min: preclinical and clinical studies. Anticancer Res. 2003; 23: 363-398. |
| [56] | Bharti AC, Takada Y, Aggarwal BB Curcumin (diferuloylmethane) inhibits receptor activator of NF-κB ligand-induced NF-κB activation in osteo-clast precursors and suppresses osteoclastogenesis. J Immunol. 2004; 172: 5940-5947. |
| [57] | Teiten MN, Dicato M, Diederich V Curcumin as a regulator of epige-netic events. Mol Nutr Food Res. 2013; 57: 1619-1629. |
| [58] | Mithu VS, Sarkar B, Bhowmik D, Das AK, Chandrakesan M, Maity S, Madhu PK Curcumin alters the salt bridge-containing turn region in amyloid (1-42) aggregates. The Journal of Biological Chemistry. 2014; 289: 11122-11131. |
| [59] | Ishimura H, Kadoya R, Suzuki T, Murakawa T, Shulga S, Kurita N Specific interactions between amyloid-β peptide and curcumin derivatives: Ab initio molecular simulations. Chemical Physics Letters. 2015; 633: 139-145. |
| [60] | US Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870. 100. Washington: US EPA; 2012. |
| [61] | Vorobjova TM Role of limbic and reticular systems in self stimulation. Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova. 1969; 19: 680-686. |
| [62] | Bureš J, Petráň M, Zachar J Electrophysiological methods in biological research. Publishing House of the Czechoslovak Academy of Sciences, Prague. 1960: 528. |
| [63] | Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997; 15: 1867-1876. |
| [64] | Bakker JM, Kavelaars A, Kamphuis PJ, Cobelens PM, van Vugt HH, van Bel F, Heijnen CJ Neonatal dexamethasone treatment increases suscepti-bility to experimental autoimmune disease in adult rats. J Immunol. 2000; 165: 5932-5937. |
| [65] | Lowry OH, Rosebrough NJ, Farr AL, Randall RJ Protein measure-ment with Folin phenol reagent. J Biol Chem. 1951; 193: 265-275. |
| [66] | 66. Gasteiger E, Hoogland C, Gattiker A Duvaud S., Wilkins M. R., Ap-pel R. D., Bairoch A. Protein identification and analysis tools on the ExPASy server; (In) John M. Walker (ed): The Proteomics Protocols Handbook, Hu-mana Press. 2005: 571-607. |
| [67] | Ashokan KV, Mundaganur DS, Mundaganur YD. Catalase: phylo-genetic characterization to explore protein cluster. J. Res. Bioinformatics. 2010; 1: 1-8. |
| [68] | Sokolik VV Protein is coded in genome and synthesized in ribosomes as a structural template of a rotameric version sequence of peptide bound con-figuration. The International Moscow Conference on Computational Molecular Biology. |
| [69] | Brooks BR, Brooks CL, Mackerell AD, Nilsson L CHARMM: the biomolecular simulation program. J Comput Chem. 2009; 30: 1545-1614. |
| [70] | Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, Shirts MR GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013; 29: 845-854. |
| [71] | Molecular modeling, 3rd Ed. Höltje H-D, Sippl W, Rognan D, Folkers G John Wiley & Sons, Hoboken NJ 2008: 320. |
| [72] | Protein ligand docking and virtual screening with GOLD. Cole J, Niessink J, Taylor R. In Virtual Screening in Drug Discovery (Eds. J. Alvarez, B. Shoichet), Taylor & Francis CRC Press, Boca Raton, Florida, USA. 2005. |
| [73] | DeLano WL. The PyMOL molecular graphics system. DeLano Scien-tific, San Carlos, CA, USA 2002. |
| [74] | Sokolik VV, Maltsev AV Cytokines neuroinflammatory reaction to β-amyloid 1-40 action in homoaggregatic and liposomal forms in rats. Biomed Chem. 2015; 9: 220-225. |
| [75] | Stacklies W, Seifert C, Graeter F Implementation of force distribu-tion analysis for molecular dynamics simulations. BMC Bioinformatics. 2011; 101: 1-5. |
| [76] | Venselaar H, Krieger E, Vriend G Homology modeling. Structural Bioinformatics. 2nd Edition. Wiley-Blackwell, Hoboken. 2009: 715-736. |
| [77] | Samofalova DA, Karpov PA, Blume YB Bioinformatic comparison of human and higher plant phosphatomes. Citol Genet. 2015; 49: 207-219. |
| [78] | Fändrich M, Schmidt M, Grigorieff N Recent progress in understand-ing Alzheimer’s β-amyloid structures. Trends Biochem Sci. 2011; 36: 338-345. |
| [79] | Sadigh-Eteghad S, Sabermarouf B, Majdi A J Amyloid-Beta: A Crucial Factor in Alzheimer’s Disease. Med Princ Pract. 2015; 24: 1-10. |
| [80] | Ridolfi E, Barone C, Scarpini E, Galimberti D The role of the innate immune system in Alzheimer’s disease and frontotemporal lobar degeneration: an eye on microglia. Clin Dev Immunol. 2013: 939786. |
| [81] | Boutajangout A, Wisniewski T The innate immune system in Alzheimer’s disease. Int J Cell Biol. 2013: 576383. |
| [82] | Combs CK, Karlo JC, Kao S-C β-Amyloid stimulation of microglia and monocytes results in TNFα-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. Journal of Neuroscience. 2001; 21: 1179-1188. |
| [83] | Smith JA, Das A, Ray SK, Banik NL Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin. 2012; 87: 10-20. |
| [84] | Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T Inflammation in Alzheimer's disease: amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors. Progress in Neurobiology. 2009; 87: 181-194. |
| [85] | Hasima N, Aggarwal BB Targeting proteasomal pathways by dietary curcumin for cancer prevention and treatment. Curr Med Chem. 2014; 21: 1583-1594. |
| [86] | Aggarwal BB, Gupta SC, Sung B Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 2013; 169: 1672-1692. |
| [87] | Plummer SM, Holloway KA, Manson MM Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex. Oncogene. 1999; 18: 6013-6020. |
| [88] | Jobin CC, Bradham A, Russo MP, Juma B Curcumin blocks cyto-kine-mediated NF-κB activation and proinflammatory gene expression by in-hibiting inhibitory factor IB kinase activity. J Immunol. 1999; 163: 3474-3483. |
| [89] | Pan MH, Lin-Shiau SY, Lin JK Comparative studies on the suppres-sion of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IB kinase and NF-κB activation in macrophages. Biochem Pharmacol. 2000; 60: 1665-1676. |
| [90] | Banerjee R. Effect of curcumin on the metal ion induced fibrillization of Amyloid-β peptide. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2014; 117: 798-800. |
| [91] | Liu KN, Lai CM, Lee YT, Wang SN, Chen RP, Jan JS, Liu HS, Wang SS Curcumin’s pre-incubation temperature affects its inhibitory potency toward amyloid fibrillation and fibrilinduced cytotoxicity of lysozyme. Biochimica et Biophysica Acta. 2012; 1820: 1774-1786. |
| [92] | Reinke AA, Gestwicki JE Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: Influence of linker length and flexibility. Chemical Biology & Drug Design. 2007; 70: 206-215. |
| [93] | Yang FS, Lim GP, Begum AN, Ubeda OJ, Simmons MR Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry. 2005; 280: 5892-5901. |
| [94] | Airoldi C, Zona C, Sironi E, Colombo L Curcumin derivatives as new ligands of A beta peptides. Journal of Biotechnology. 2011; 156: 317-324. |
| [95] | Mourtas S, Canovi M, Zona C Curcumin-decorated nanoliposomes with very high affinity for amyloid-β 1-42 peptide. Biomaterials. 2011; 32: 1635-1645. |
| [96] | Taylor M, Moore S, Mourtas S, Niarakis A Effect of curcumin associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer’s Aβ peptide. Nanomedicine-Nanotechnology Biology and Medi-cine. 2011; 7: 541-550. |
| [97] | Kozmon S, Tvaroska I Molecular dynamic studies of amyloid-beta interactions with curcumin and Cu2+ ions. Chemical Papers. 2015; 69: 1262-1276. |
| [98] | Zhao LN, Chiu S-W, Benoit J, Chew LY, Mu YG The effect of cur-cumin on the stability of Aβ dimers. The Journal of Physical Chemistry B. 2012; 116: 7428-7435. |
APA Style
Victoria V. Sokolik, Pavel A. Karpov, Dariya A. Samofalova, Sergiy M. Shulga. (2016). Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP. Advances in Biochemistry, 4(4), 34-46. https://doi.org/10.11648/j.ab.20160404.11
ACS Style
Victoria V. Sokolik; Pavel A. Karpov; Dariya A. Samofalova; Sergiy M. Shulga. Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP. Adv. Biochem. 2016, 4(4), 34-46. doi: 10.11648/j.ab.20160404.11
AMA Style
Victoria V. Sokolik, Pavel A. Karpov, Dariya A. Samofalova, Sergiy M. Shulga. Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP. Adv Biochem. 2016;4(4):34-46. doi: 10.11648/j.ab.20160404.11
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ab.20160404.11,
author = {Victoria V. Sokolik and Pavel A. Karpov and Dariya A. Samofalova and Sergiy M. Shulga},
title = {Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP},
journal = {Advances in Biochemistry},
volume = {4},
number = {4},
pages = {34-46},
doi = {10.11648/j.ab.20160404.11},
url = {https://doi.org/10.11648/j.ab.20160404.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20160404.11},
abstract = {Since it has been shown that Alzheimer’s disease is accompanied by higher peripheral concentrations of cytokines, we focused on the correction of chronic inflammation causing Aβ excess and aggregation what should have a positive impact. Proinflammatory cytokines action is realized by NF-κB intracellular signals. Curcumin can inhibit activation of the proinflammatory transcription factor NF-κB and is able to be mounted in the amyloid-β fibrils and encourage their disaggregation. To study the influence of anti-inflammatory effect of curcumin and its ability to model complexes with a fragment of AβPP. Investigation was carried out on rats with model of Alzheimer’s disease using nasal therapy with curcumin Concentration of cytokines in cerebral cortex, hippocampus and blood serum, and indicators of conditioned active escape reflex were determined in this study. Methods of molecular dynamics and docking were used to examine the interactions of curcumin with fragment of AβPP. Аβ42_Human in the hippocampus of rats provoked chronic neuroinflammation specifically and primarily at the injection site. Curcumin performance revealed specific depressing effect on cytokines in the cerebral cortex and in the hippocampus it appeared similar to the above, but of lower level. Anti-inflammatory activity of curcumin led to the recovery of memory parameters. Analysis of restriction sites of AβPP has shown that position of curcumin in Site II is energetically more favorable for binding. Our suggestion that curcumin is an effective anti-cytokine factor was confirmed by experimental results obtained in vivo and explain the mechanism describing its effect on NF-κB Curcumin doesn’t block the excision Aβ but binding with its hydrophobic region.},
year = {2016}
}
TY - JOUR T1 - Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP AU - Victoria V. Sokolik AU - Pavel A. Karpov AU - Dariya A. Samofalova AU - Sergiy M. Shulga Y1 - 2016/06/20 PY - 2016 N1 - https://doi.org/10.11648/j.ab.20160404.11 DO - 10.11648/j.ab.20160404.11 T2 - Advances in Biochemistry JF - Advances in Biochemistry JO - Advances in Biochemistry SP - 34 EP - 46 PB - Science Publishing Group SN - 2329-0862 UR - https://doi.org/10.11648/j.ab.20160404.11 AB - Since it has been shown that Alzheimer’s disease is accompanied by higher peripheral concentrations of cytokines, we focused on the correction of chronic inflammation causing Aβ excess and aggregation what should have a positive impact. Proinflammatory cytokines action is realized by NF-κB intracellular signals. Curcumin can inhibit activation of the proinflammatory transcription factor NF-κB and is able to be mounted in the amyloid-β fibrils and encourage their disaggregation. To study the influence of anti-inflammatory effect of curcumin and its ability to model complexes with a fragment of AβPP. Investigation was carried out on rats with model of Alzheimer’s disease using nasal therapy with curcumin Concentration of cytokines in cerebral cortex, hippocampus and blood serum, and indicators of conditioned active escape reflex were determined in this study. Methods of molecular dynamics and docking were used to examine the interactions of curcumin with fragment of AβPP. Аβ42_Human in the hippocampus of rats provoked chronic neuroinflammation specifically and primarily at the injection site. Curcumin performance revealed specific depressing effect on cytokines in the cerebral cortex and in the hippocampus it appeared similar to the above, but of lower level. Anti-inflammatory activity of curcumin led to the recovery of memory parameters. Analysis of restriction sites of AβPP has shown that position of curcumin in Site II is energetically more favorable for binding. Our suggestion that curcumin is an effective anti-cytokine factor was confirmed by experimental results obtained in vivo and explain the mechanism describing its effect on NF-κB Curcumin doesn’t block the excision Aβ but binding with its hydrophobic region. VL - 4 IS - 4 ER -
Information
Email: