화향수(化香樹) 수피(樹皮)의 메탄올 추출물이 신경세포에서 아밀로이드 전구단백질의 대사에 미치는 영향

Effects of MeOH Extract from Stem Bark of Plantocracy strobilacea on the Metabolism of Amyloid Precursor Protein in Neuroblastoma Cells

  • 투고 : 2013.01.04
  • 심사 : 2013.02.21
  • 발행 : 2013.02.25

초록

Alzheimer's disease (AD), one of the most common forms of dementia, is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides of 40-42 residues, which are generated by processing of amyloid precursor protein (APP). $A{\beta}$ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. Here, we show that MeOH extract from stem bark of Platycarya strobilacea Sieb. et. Zucc. (PSM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that PSM may regulate the processing of APP and increase the sAPP${\alpha}$. PSM does not change the protein level of presenilin and nicastrin, however, it reduces the protein expression level of BACE1. In addition, PSM reduces the secretion level of $A{\beta}42$ and $A{\beta}40$ from the cell line without toxicity. We suggest that Platycarya strobilacea may be useful as a herbal medicine to treat Alzheimer's disease.

키워드

참고문헌

  1. Vellas, B. and Fitten, L.J. Research and practice in Alzheimer's disease. Springer Publishing Co. 2000.
  2. Morris, J.C. Classification of dementia and Alzheimer's disease. Acta Neurol. Scand. 165: 41-50, 1996.
  3. Braak, H., Braak, E. and Strothjohann, M. Abnormally phosphorylated tau protein related to the formation of neurofibrillary tangles and neuropil threads in the cerebral cortex of sheep and goat. Neurosci Lett. 171: 1-4, 1994. https://doi.org/10.1016/0304-3940(94)90589-4
  4. Kang, J., Lemaire, H.G., Unterbeck, A., Salbaum, J.M., Masters, C.L., Grzeschik, K.H., Multhaup, G., Beyreuther, K., Muller-Hill, B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733-736, 1987. https://doi.org/10.1038/325733a0
  5. Vassar, R., Bennett, B.D., Babu-Khan, S., Kahn, S., Mendiaz, E.A., Denis, P., Teplow, D.B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M.A., Biere, A.L., Curran, E., Burgess, T., Louis, J.C., Collins, F., Treanor, J., Rogers, G., Citron, M. $\beta$-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286: 735-741, 1999. https://doi.org/10.1126/science.286.5440.735
  6. Selkoe, D.J. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399: 23-31, 1999. https://doi.org/10.1038/19866
  7. Fu, H., Dou, J., Li, W., Cui, W., Mak, S., Hu, Q., Luo, J., Lam, C.S., Pang, Y., Youdim, M.B. and Han, Y. Promising multifunctional anti-Alzheimer's dimer bis(7)-Cognitin acting as an activator of protein kinase C regulates activities of alpha-secretase and BACE-1 concurrently. Eur. J. Pharmacol. 623(1-3):14-21, 2009. https://doi.org/10.1016/j.ejphar.2009.09.013
  8. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y.Q., Rogaeva, E., Chen, F., Kawarai, T., Supala, A., Levesque, L., Yu, H., Yang, D.S., Holmes, E., Milman, P., Liang, Y., Zhang, D.M., Xu, D.H., Sato, C., Rogaev, E., Smith, M., Janus, C., Zhang, Y., Aebersold, R.,Farrer, L.S., Sorbi, S., Bruni, A., Fraser, P., St. George-Hyslop, P. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407: 48-54, 2000. https://doi.org/10.1038/35024009
  9. Lee, S.F., Shah, S., Li, H., Yu, C., Han, W., Yu, G Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. J. Biol. Chem. 277: 45013-45019, 2002. https://doi.org/10.1074/jbc.M208164200
  10. Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M. and Haass, C. PEN-2 is an integral component of the $\gamma$-secretase complex required for coordinated expression of presenilin and nicastrin. J. Biol. Chem. 277: 39062-39061, 2002. https://doi.org/10.1074/jbc.C200469200
  11. Hardy, J. and Selkoe, D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297: 353-356, 2002. https://doi.org/10.1126/science.1072994
  12. Cai, H., Wang, Y., McCarthy, D., Wen, H., Borchelt, D.R., Price, D.L., Wong, P.C. BACE1 is the major $\beta$-secretase for generation of A$\beta$ peptides by neurons. Nature Neurosci. 4: 233-234, 2001. https://doi.org/10.1038/85064
  13. Sugimoto, H. Donepezil hydrochloride. a treatment drug for Alzheimer's disease. Chem. Rec. 1: 63-73, 2001. https://doi.org/10.1002/1528-0691(2001)1:1<63::AID-TCR9>3.0.CO;2-J
  14. Zarotsky, V., Sramek, J.J. and Cutler, N.R. Galantamine hydrobromide. an agent for Alzheimer's disease. Am. J. Health Syst. Pharm. 60: 446-452, 2003.
  15. Jann, M.W. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy. 20: 1-12, 2000. https://doi.org/10.1592/phco.20.1.1.34664
  16. Babu, D., Lee, J.S., Park, S.Y., Thapa, D., Choi, M.K., Kim, A.R., Park, Y.J., Kim, J.A. Involvement of NF-kappaB in the inhibitory actions of Platycarya strobilacea on the TNF-alpha-induced monocyte adhesion to colon epithelial cells and chemokine expression. Arch Pharm Res. 31(6):727-735, 2008. https://doi.org/10.1007/s12272-001-1219-0
  17. Kim, Y.H., Kim, K.H., Han, C.S., Yang, H.C., Park, S.H., Jang, H.I., Kim, J.W., Choi, Y.S., Lee, N.H. Anti-wrinkle activity of Platycarya strobilacea extract and its application as a cosmeceutical ingredient. J. Cosmet. Sci. 61(3):211-224, 2010.
  18. Wang, R., Sweeney, D., Gandy, S.E. and Sissodia, S.S. The profile of soluble amyloid $\beta$ protein in cultured cell media. J. Biol. Chem. 271: 31894-31902, 1996. https://doi.org/10.1074/jbc.271.50.31894
  19. Tung, J.S., Davis, D.L., Anderson, J.P., Walker, D.E., Mamo, S., Jewett, N., Hom, R.K., Sinha, S., Thorsett, E.D., John, V. Design of substrate-based inhibitors of human beta-secretase. J. Med. Chem. 45: 259-262, 2002. https://doi.org/10.1021/jm0155695
  20. Leem, J.Y., Saura, C.A., Pietrzik, C., Christianson, J., Wanamaker, C., King, L.T., Veselits, M.L., Tomita, T., Gasparini, L., Iwatsubo, T., Xu, H., Green, W.N., Koo, E.H., Thinakaran, G. A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface. Neurobiol. Dis. 11: 64-82, 2002. https://doi.org/10.1006/nbdi.2002.0546
  21. Iqbal, K., Sisodia, S.S. and Winblad, B. Alzheimer's disease. Advances in etionlogy, pathogenesis and therapeutics. John Wiley & Sons, Ltd. 2001.
  22. 구진숙, 서부일, 박지하, 노성수. 치매 치료 한약(처방 및 한약재) 연구 논문 동향 분석. 大韓本草學會誌 25(3):131-137, 2010.
  23. 김상태, 강형원, 한평림, 조형권, 김태헌, 류영수, 손형진. 壯元丸加減方인 LMK02가 아밀로이드 前驅蛋白質으로 形質轉換 된 초파리에 미치는 효과. 동의신경정신과학회지 19(2):151-163, 2008.
  24. Skovronsky, D.M., Moore, D.B., Milla, M.E., Doms, R.W., Lee, V.M. Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J. Biol. Chem. 275: 2568-2575, 2000. https://doi.org/10.1074/jbc.275.4.2568
  25. Nunan, J., Small, D.H. Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett. 483: 6-10, 2000. https://doi.org/10.1016/S0014-5793(00)02076-7
  26. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., Kholodenko, D., Motter, R., Sherrington, R., Perry, B., Yao, H., Strome, R., Lieberburg, I., Rommens, J., Kim, S., Schenk, D., Fraser, P., St George Hyslop, P. and Selkoe. D.J. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 3: 67-72, 1997. https://doi.org/10.1038/nm0197-67
  27. Obregon, D., Hou, H., Deng, J., Giunta, B., Tian, J., Darlington, D., Shahaduzzaman, M., Zhu, Y., Mori, T., Mattson, M.P., Tan, J. Soluble amyloid precursor protein-$\alpha$ modulates $\beta$-secretase activity and amyloid-$\beta$ generation. Nat Commun. 3: 777, 2012. https://doi.org/10.1038/ncomms1781