소식지 주소 : 부산광역시금정구부산대학로 63번길 2( 장전동 ) 부산대학교약학대학 / 전화 :051)510-2814 팩스 :051)518-2821 E-mail:agingbank@pusan.ac.kr hyjung@pusan.ac.kr Homepage : http://knrrb.knrrc.or.kr/ http://aging.pharm.pusan.ac.kr/ Content 6 월호 알기쉬운노화의기초지식 아세틸콜린에스터라아제 (AChE) 억제제와 β-site APP 단백질분해효소 (BACE1) 억제제를통한알츠하이머병 (Alzheimer s disease) 의치료전략 2018 년 6 월호 정희진박사 ( 분자염증노화제어연구센터 ) 발행인 : 정해영 발행처 : 한국연구재단지원 알츠하이머병 (Alzheimer s disease, AD) 편집인 : 정희진, 방은진, 김병무, 임수경 β 1
Aging Tissue Bank β β 아밀로이드증폭가설 (Amyloid cascade hypothesis) β γ β β β 그림 1. 알츠하이머병의아밀로이드베타의단백분해효소경과과정 2
Aging Tissue Bank 치료표적으로서의 Aβ β β β β β β β β γ β β β β β 3
Aging Tissue Bank 그림 2. 콜린에스터라아제저해제와 BACE1 저해제의작용메커니즘 천연소재로부터의치료제 α 4
Aging Tissue Bank O O HO OCH 3 OCH 3 Curcumin HO O HO O O EGCG Resveratrol 그림 3. 천연소재의화학적구조 참고문헌 5
Aging Tissue Bank 피부염증과노화를조절하는 PAR2 의역할과기능 n Protease activated receptor 2 (PAR 2) n PAR2 in skin inflammation <Keratinocyte 에서 PAR2 의활성과기능 > 6
Aging Tissue Bank PPARγ 작용제의산화스트레스조절 γ γ γ γ γ γ https://actitudsaludable.net/alimentacion-contra-el-envejecimiento/envejecimiento-1 7
Aging Tissue Bank <은 행 동 향> 세미나 개최 1. 초청세미나 장소 및 일자 : 2018년 4월 13일 (금요일) / 부산대 약대 세미나실 연 제 : Macroautophagy Enhanced by Mitochondrial Respiration Remodels Vacuole Liquid-Ordered Membrane Domain to Control Micro-Liphophagy 연 자 : Arnold Y. Seo Ph.D. (Janelia Research Campus, USA) 연 제 : Melanocortin 3 receptor (MC3R), a novel regulator of hepatic autophagy in obesity 연 자 : Joo Yun Jun Ph.D. (National Institutes of Health, USA) 연 제 : Inhibition of Drp1 Ameliorates Synaptic Depression, Aβ Deposition, and Cognitive Impairment in an Alzheimer's Disease Model 연 자 : 조 동 규 교수 (성균관대학교 약학대학 ) 2. 초청세미나 장소 및 일자 : 2018년 5월 31일 (목요일) / 부산대 약대 세미나실 연 제 : 오체사성학(체질의학)에 따른 성품 형성과 노화 진행기전 연 자 : 고 창 학 박사 (사상/오체사성학회 총회장) 8
Aging Tissue Bank 노화조직을활용한최근연구논문 1. Chung, K.W., Lee, E.K., Lee, M.K., Oh, G.T., Yu, B.P., Chung, H.Y.: Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging. J Amer Soc Nephrol, 29(4):1223-1237 (2018) 2. Jung, H.J., Lee, M.J., Park, Y.J., Noh, S.G., Lee, A.K., Moon, K.M., Lee, E.K., Bang, E.J., Park, Y.J., Kim, S.J., Yang, J., Ullah, S., Chun, P., Jung, Y.S., Moon, H.R., Chung, H.Y.:A novel synthetic compound, (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-iminothiazolidin-4-one (MHY773) inhibits mushroom tyrosinase. Biosci Biotechnol Biochem, 1-9 (2018) 3. Kim, Y., Kwon, O.K., Chae, S., Jung, H.J., Ahn, S., Jeon, J.M., Sung, E., Kim, S., Ki, S.H., Chung, K.W., Chung, H.Y., Jung, Y.S., Hwang, D.H., Lee, S.: Quantitative Proteomic Analysis of Changes Related to Age and Calorie Restriction in Rat Liver Tissue. Proteomics, 18(5-6):e1700240 (2018) 4. Kim, M.J., An, H.J., Kim, D.H., Lee, B., Lee, H.J., Ullah, S., Kim, S.J., Jeong, H.O., Moon, K.M., Lee, E.K., Yang, J., Akter, J., Chun, P., Moon, H.R., Chung, H.Y.: Novel SIRT1 activator MHY2233 improves glucose tolerance and reduces hepatic lipid accumulation in db/db mice. Bioorg Med Chem Lett, 28(4):684-688(2018) 5. Chung, K.W., Jeong, H.O., Lee, E.K., Kim, S.J., Chun, P., Chung, H.Y., Moon, H.R.: Evaluation of Antimelanogenic Activity and Mechanism of Galangin in Silico and in Vivo. Biol Pharm Bull, 41(1):73-79 (2018) 6. An, H.J., Lee, B., Kim, S.M., Kim, D.H., Chung, K.W., Ha, S.G., Park, K.C., Park, Y.J., Kim, S.J., Yun, H.Y., Chun, P., Yu, B.P., Moon, H.R., Chung, H.Y.: A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation. Biol Pharm Bull, 41(1):29-35(2018) 7. Kim, K.M., Chung, K.W., Jeong, H.O., Lee, B., Kim, D.H., Park JW, Kim SM, Yu, B.P., Chung, H.Y.: MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction. Oncotarget, 9(5):5588-5599(2017) 8. Lee, E.K., Jeong, H.O., Bang, E.J., Kim, C.H., Mun, J.Y., Noh, S., Gim, J.A., Kim, D.H., Chung, K.W., Yu, B.P., Chung, H.Y.:The involvement of serum exosomal mir-500-3p and mir-770-3p in aging: modulation by calorie restriction. Oncotarget, 9(5):5578-5587(2017) 9. Jung, H.J., Seong, S.H., Ali, M.Y., Min, B.S., Jung, H.A., Choi, J.S.: α-methyl artoflavanocoumarin from Juniperus chinensis exerts anti-diabetic effects by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in insulin-resistant HepG2 cells. Arch Pharm Res, 40(12):1403-1413(2017) 9
Aging Tissue Bank 10. Abdul, Q.A., Yu, B.P., Chung, H.Y., Jung HA., Choi, J.S.: Epigenetic modifications of gene expression by lifestyle and environment. Arch Pharm Res, 40(11):1219-1237(2017) 11. Park, G.C., Kim, J.M., Park, H.Y., Han, J.M., Shin, S.C., Jang, J.Y., Jung, D.W., Kim, I.J., Lee, J.C., Lee, B.J.: TSH-independent release of thyroid hormones through cold exposure in aging rats. Oncotarget, 8(52):89431-89438(2017) 12. Kim, D.H., Kim, S.M., Lee, B., Lee, E.K., Chung, K.W., Moon, K.M., An, H.J., Kim, K.M,. Yu, B.P., Chung, H.Y.: Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome. J Nutr Biochem, 45:104-114(2017) 13. Lee, E.K., Chung, K.W., Kim, Y.R., Ha, S., Kim, S.D., Kim, D.H., Jung, K.J., Lee, B., Im, E., Yu, B.P., Chung, H.Y. : Small RNAs induce the activation of the pro-inflammatory TLR7 signaling pathway in aged rat kidney. Aging Cell, 16(5):1026-1034(2017) 14. Hwang, S.Y., Kang, Y.J., Sung, B., Jang, J.Y., Hwang, N.L., Oh, H.J., Ahn, Y.R., Kim, H.J., Shin, J., Yoo, M.A., Kim, C.M., Chung, H.Y., Kim, N.D.: Folic Acid is Necessary for Proliferation and Differentiation of C2C12 Myoblasts. J Cell Physiol, 233(2):736-747(2017). 15. Kim, S.M., Lee, B., An, H.J., Kim, D.H., Park, K.C., Noh, S.G., Chung, K.W., Lee, E.K., Kim, K.M., Kim, D.H., Kim, S.J., Chun, P., Lee, H.J., Moon, H.R., Chung, H.Y.: Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging. Oncotarget, 8(28), 46273-46285(2017). 16. Chung, K.W., Kim, K.M., Choi, Y.J., An, H.J., Lee, B., Kim, D.H., Lee, E.K., Im, E., Lee, J., Im, D.S., Yu, B.P., Chung, H.Y.:The critical role played by endotoxin-induced liver autophagy in the maintenance of lipid metabolism during sepsis Autophagy 13(7), 1113-1129(2017). 17. Park, C.H., Shin, S.H., Lee, E.K., Kim, D.H., Kim, M.J., Roh, S.S., Yokozawa, T., Chung, H.Y.:Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation. Phytother Res, 31(5):721-728(2017) 18. Kim, Y.R., Lee, E.K., Kim, D.H., Kim, K.M., Lee, B., An, H.J., Park, J.W., Moon, K.M., Park, M.H., Chung, K.W., Park, J.Y., Kim, S.J., Yun, H.Y., Son, S., Chun, P., Moon, H.R., Chung, H.Y.:PPARα activation by MHY908 attenuates age-related renal inflammation through modulation of the ROS/Akt/FoxO1 pathway. Exp Gerontol, pii: S0531-5565(16)30288-1(2017) 19. An, H. J., Lee, B., Kim, D.H., Lee, E.K., Chung, K.W., Park, M.H., Jeong, H.O., Kim, S.M., Moon, K.M., Kim, Y.R., Kim, S.J., Yun, H.Y., Chun, P., Yu, B.P., Moon, H.R., Chung, H.Y.: Physiological characterization of a novel PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl) -2-methylphenoxy)-2-methy lpropanoic acid (MHY2013). Oncotarget, 8(10),16912-16924(2017) 10
Aging Tissue Bank < 홍보 > 노화 수명연장연구에필요한시료를찾으십니까? 부산대 Aging Tissue Bank 로오십시오 본은연구자들에게노화기전및노화제어에필요한연구시료와정보를 신속하게제공하여노화연구를원활히지원하는것을목적으로하고있습니다. 노화조직과노화쥐이미지 1) 노화조직의연구소재분양 1. 자유식이 Sprague Dawley(SD) rat(al) 연령별노화조직 2. 식이제한 SD rat(cr) 연령별노화조직 3. LPS 처리노화조직 (SD rat) 4. AAPH 처리노화조직 (F344 rat) 5. 자유식이 C57BL/6 mouse 연령별노화조직 6. 유전자변이모델동물 (GH 결손, mini rat) 조직 7. 노화촉진모델동물 (SMP30 유전자변이마우스 ) 8. 각종항산화물질투여노화조직 (SD rat) 구체적인것은 homepage 를방문하시기를바랍니다. www.agingbank.or.kr http://agingbank.pharm.pusan.ac.kr 2) 노화관련 Data Base 구축을통한통합정보제공 a) http://aging.pharm.pusan.ac.kr b) http://bionet.inje.ac.kr/massprophet c) http://bionet.inje.ac.kr/trep_db d) http://aging.pharm.pusan.ac.kr/agingdb e) http://aging.pharm.pusan.ac.kr:8080/dbpiat 연구소재가필요하시면다음으로연락주십시오 Tel : 051-510-2814 Fax : 051-518-2821 E-mail: agingbank@pusan.ac.kr; hyjung@pusan.ac.kr 11
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