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蕭永基（Shiao, Young-Ji）

Shiao, Young-Ji

姓名： 蕭永基（Shiao, Young-Ji）
職稱： 研究員
電話： 2820-1999轉4171、4163
E-mail : yshiao@nricm.edu.tw

學歷
國立清華大學　生命科學研究所　博士
主要經歷
加拿大亞伯達大學　脂質及脂蛋白研究組　博士後研究

專長
細胞生物學，生物化學，神經科學

研究簡介
    阿滋海默氏症又稱為老年失智症。老年失智症之致病原因與病情進展一般認為與神經元的兩種病理變化有關。這兩種病理變化分別是神經元外的老年瘢(senile plaques)及神經元內的神經纖維纏結 (neurofibrillary tangle)。目前並沒有有效的治療方式可以停止或逆轉老年失智症之病情進展。有關老年失智症之分子機制，其瞭解也極為有限。由於老年失智症病人腦中的不正常摺疊的A蛋白累積，此病症已被認知為蛋白錯誤摺疊疾病。A蛋白是由膜蛋白APP經不正常截切而產生的短胜肽副產物。具有短區域板狀的A單體可溶於水。然而，在單體濃度足夠高時，它們會發生戲劇性的構形變化而形成大區域板狀的三級結構而聚集形成澱粉樣纖維。澱粉樣纖維沉積於神經元外，便形成老年瘢。另一方面，由於神經元內與微小管結合的Tau蛋白過度磷酸化與不正常聚集形成神經纖維纏結與造成神經突之營養失調，因此老年失智症也被認定是一種Tau蛋白病。中藥在防治老年失智症方面，因副作用少與功能多元性而有較強的優勢。臨床主要使用補腎，調理心脾，活血化瘀，安神健腦開竅的中藥。目前研究已指出多種單、複方的中藥具有治療老年癡呆症的潛力。本實驗室的長期目標即為深入瞭解老年癡呆症之致病機制，及探討如何利
用中草藥來治療老年失智症。

期刊論文: 限所內研究人員(用Email)點選編輯點此編輯

NCBI PubMed :  Young-Ji Shiao (Please click!!)
  1. Chen Y.-X., Le P.-T.-N., Tzeng T.-T., Tran T.-H., Nguyen A.-T., Cheng I.-H.-J., Huang C.-Y.-F.*, Shiao Y.-J.*, Ching T.-T.* (2021) Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems. Nutrients 13, 4317.
  2. Tsay H.-J., Liu H.-K., Kuo Y.-H., Chiu C.-S., Liang C.-C., Chung C.-W., Chen C.-C., Chen Y.-P., Shiao Y.-J.* (2021) EK100 and Antrodin C Improve Brain Amyloid Pathology in APP/PS1 Transgenic Mice by Promoting Microglial and Perivascular Clearance Pathways. International Journal of Molecular Sciences 22(19):10413.
  3. Huang H.-J., Wang H.-T., Yeh T.-Y., Lin B.-W., Shiao Y.-J., Lo Y.-L., Lin A.-M. (2021) Neuroprotective effect of selumetinib on acrolein-induced neurotoxicity. Scitific Report 14;11(1):12497.
  4. Hsu W.-H., Huang N.-K., Shiao Y.-J., Lu C.-K., Chao Y.-M., Huang Y.-J., Yeh C.-H., Lin Y.-L. (2021) Gastrodiae rhizoma attenuates brain aging via promoting neuritogenesis and neurodifferentiation. Phytomedicine. 87:153576.
  5. Hsu W.-S.#, Shiao Y.-J.#, ChaoY.-M., Huang Y.-J., Yeh C.-H., Lin Y.-L. (2020) T1-11, a dual-function adenosine derivative, ameliorates D-galactose–induced aging in mice. Aging 12, 10556. # Contribution equally.
  6. Tseng H.-J., Lin M.-H., Shiao Y.-J., Yang Y.-C., Chu J.-C., Chen C.-Y., Chen Y.-Y., Lin T.-E., Su C.-J., Pan S.-L., Chen L.-C., Wang C.-Y., Hsua K.-C., Huang W.-J. (2020) Synthesis and biological evaluation of acridine-based histone deacetylase inhibitors as multitarget agents against Alzheimer’s disease. European Journal of Medicinal Chemistry 192, 112193.
  7. Yeh S.-H.-H, Shie F.-S., Liu H.-K., Yao H.-H., Kao P.-C., Lee Y.-H., Chen L.-M., Hsu S.-M., Chao L.-J., Wu K.-W., Shiao Y.-J. *, Tsay H.-J. * (2020) A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice. Neurobiology of Aging 90, 60-74.
  8. Wu P.-C., Fann M.-J., Tran T.-T., Chen S.-C., Devina T., Cheng I.-H., Lien C.-C., Kao L.-S., Wang S.-J., Fuh J.-L., Tzeng T.-T., Huang C.-Y., Shiao Y.-J.*, Wong Y.-H. * (2019) Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons. Scitific Report 17;9(1):19301.
  9. Lin, L.-C., Lee, L.-C., Huang, C., Chen, C.-T., Song, J.-S., Shiao, Y.-J., Liu, H.-K. (2019) Effects of boschnaloside from Boschniakia rossica on dysglycemia and islet dysfunction in severely diabetic mice through modulating the action of glucagon-like peptide-1. Phytomedicine 62:152946.
  10. Chen, Y.-J., Hsu, C.-C., Shiao, Y.-J., Wang, H.-T., Lo, Y.-L., Lin, A.M.Y. (2019) Anti-inflammatory effect of afatinib (an EGFR-TKI) on OGD-induced neuroinflammation. Scientific Reports 9(1):2516.
  11. Hsu, W.-H., Shen, Y.-C., Shiao, Y.-J., Kuo, C.-H., Tseng, Y.-F.-J., Lin, T.-Y., Ku, W.-C., and Lin, Y.-L. (2019) Combined proteomic and metabolomic analyses of cerebrospinal fluid from mice with ischemic stroke reveals the effects of a Buyang Huanwu decoction in neurodegenerative disease. PLoS One 14(1):e0209184.
  12. Lee, Y.-H., Hsu, H.-C., Kao, P.-C., Shiao, Y.-J., Yeh, S.-H., Shie, F.-S., Hsu, S.-M., Yeh, C.-W., Liu, H.-K., Yang, S.-B., Tsay, H.-J. (2018) Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation. International Journal of Molecular Sciences 19(8), E2333.
  13. Lin, C.-F., Shiao, Y.-J., Chen, C.-C., Tzeng, T.-T., Chen, C.-C., Lee, L.-Y., Chen, W.-P., Shen, C.-C. (2018) A xanthurenate and an isoindolinone from the mycelia of Hericium erinaceum. Phytochemistry Letters 26, 218-221.
  14. Li, I.-C., Lee, L.-Y., Tzeng, T.-T., Chen, W.-P., Chen, Y.-P., Shiao, Y.-J. and Chen, C.-C. (2018) Neurohealth properties of Hericium Erinaceus mycelia enriched with erinacines. Behavior Neurology 2018, 580263.
  15. Tzeng, T.-T., Chen, C.-C., Chen, C.-C., Lee, L.-Y., Chen, W.-P., Lu, C.-K., Huang, C.-Y.-F., Shen, C.-C. and Shiao, Y.-J. * (2018) The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium Erinaceus Mycelium Ameliorate Alzheimer’s Disease-Related Pathologies in APP/PS1 Transgenic Mice. International Journal of Molecular Sciences 19(2), E598.
  16. Huang, Y.-C., Tsay, H.-J., Lu, M.-K., Lin, C.-H., Yeh, C.-W., Shie, F.-S. Liu, H.-K.* and Shiao, Y.-J.* (2017) Astragalus membranaceus-plysaccharides ameliorates obesity, hepatic steatosis, neuroinflammation and cognition impairment without affecting amyloid eposition in metabolically stressed APPswe/PS1dE9 mice. International Journal of Molecular Sciences 18(12):E2746.
  17. Yang, C,-N., Wu, M.-F., Liu, C.-C., Jung, W.-H., Chang, Y.-C., Lee, W.P., Shiao, Y.-J., Wu, C.L., Liou, H.-H., Lin, S.-K., Chan, C.-C. (2017) Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia. Human Molecular Genetics 26(20):3909-3921.
  18. Yeh, C.-W., Liu, H.-K., Lin, LC, Liou, KT, Huang, YC, Lin, CH, Tzeng, TT, Shie, FS, Tsay, HJ and Shiao, Y.-J. (2017) Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice. Journal of Ethnopharmacololgy 209: 50-61.
  19. Kuo, P.-C., Hung, H.-Y., Chuang, C.-W., Hwang, T.-L., Liao, Y.-R., Huang, S.-C., Shiao, Y.-J., Kuo, D.-H., Wu, T.-S. (2017) Anti-inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis. Molecules 22(6): E967.
  20. Shiao, Y.-J., Su, M.-H., Lin, H.-C. and Wu, C.-R. (2017) Echinacoside ameliorates memory impairment and cholinergic deficit induced by amyloid beta peptide via inhibiting amyloid deposition and toxicology. Food & Function 8(6), 2283-2294.
  21. Chen, P.-C., Tsai, W.-J., Ueng, Y.-F., Tzeng, T.-T., Chen, H.-L., Zhu, P.-R., Huang, C.-H., Shiao, Y.-J.*, Li, W.-T.* (2017) Neuroprotective and Antineuroinflammatory Effects of Hydroxyl- Functionalized Stilbenes and 2-Arylbenzo[b]furans. Journal of Medicinal Chemistry 60(9):4062-4073.
  22. Shiao, Y.-J., Su, M.-H., Lin, H.-C. and Wu, C.-R. (2017) Acteoside and Isoacteoside Protect Amyloid β Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo. International Journal of Molecular Sciences 18(4): E895.
  23. Tzeng, T.-T., Chen, C.-C., Lee, L.-Y., Chen, W.-P., Lu, C.-K., Huang, C.-Y.-F., Shen, C.-C., Chen, C.-C.* and Shiao, Y.-J.* (2016) Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer's disease-related pathologies in APPswe/PS1dE9 transgenic mice. Journal of Biomedical Science 23(1):49.
  24. Tsay, H.-J., Huang, Y.-J., Chen, Y.-J., Lee, Y.-H., Hsu, S.-M., Tsai, K.-C., Yang, C.N., Huang, F.-L., Shie, F.-S., Lee, L.-C.* and Shiao, Y.-J.* (2016) Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. Journal of Biomedical Science 23:27.
  25. Chen, C.-C., Tzeng, T.-T., Chen, C.-C., Ni, C.-L., Lee, L.-Y., Chen, W.-P., Shiao, Y.-J.,* and Shen, C.-C.* (2016) Erinacine S, a Rare Sesterterpene from the Mycelia of Hericium erinaceus. Journal of Natural Products 79(2):438-441.
  26. Shen, D.-Y., Nguyen, T.-N., Wu, S.-J., Shiao, Y.-J., Hung, H.-Y., Kuo, P.-C., Kuo, D.-H., Thang, T.-D., Wu, T.-S. (2015) γ- and δ-Lactams from the Leaves of Clausena lansium. Journal of Natural Products 78(1):2521-2530.
  27. Yeh, C.-W., Yeh, S.-H.-H., Shie, S.-F., Lai, W.-S., Liu, H.-K., Tzeng, T.-T., Tsay, H.J., Shiao, Y.-J. (2015) Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice Corresponding. Neurobiology of Aging 36(11):2948-2994.
  28. Chen, H.-J., Shen, Y.-C., Shiao, Y.-J., Liou, K.-T., Hsieh, P.-H., Lee, C.-Y., Chen, Y.-R., Lin, Y.-L. (2015) Multiplex brain proteomic analysis revealed the molecular therapeutic effects of Buyang Huanwu Decoction on cerebral ischemic stroke mice. PLoS One 10(10), e0140823.
  29. Shie, S.-F.#, Shiao, Y.-J. #, Yeh, C.-W., Lin, C.-H., Tzeng, T.-T., Hsu, H.-C., Huang, F.-L., Tsay, H.-J., Liu, H.-K. (2015) Obesity and Hepatic Steatosis are associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice. PLoS One. 10(8), e0134531. #contribution equally.
  30. Lin, Y.-L., Tsay, H.-J., Lai, T.-H., Tzeng, T.-T., Shiao, Y.-J.* (2015) Lithospermic acid attenuates MPP+-induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways. Journal of Biomedical Science 22, 37.
  31. Hsieh, J.-F., Lin, W.-J., Huang, K.-F., Liao, J.-H., Don, M.-J., Shen, C.-C., Shiao, Y.-J., Li, W.-T. (2015) Antioxidant activity and inhibition of α-glucosidase by hydroxyl-functionalized 2-arylbenzo[b]furans. European Journal of Medicinal Chemistry 93, 443-451.
  32. Tzeng, T.-T., Tsay, H.-J., Chang, L., Hsu, C.-L., Lai, Z.-H., Huang, F.-L. Shiao, Y.-J. (2013) Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid. Journal of Biomedical Science 20, 90.
  33. Tsay, H.-J., Huang, Y.-C., Huang, F.-L., Chen, C.-P., Tsai, Y.-C., Wang, Y.-H., Wu. M.-F., Chiang, F.-Y. Shiao, Y.-J. (2013) Amyloid b peptide-mediated neurotoxicity is attenuated by the proliferating microglia more potently than by the quiescent phenotype. Journal of Biomedical Science 20, 78.
  34. Wang, C.-J., Chen, C.-C., Tsay, H.-J. Chiang, F.-Y., Wu. M.-F. Shiao, Y.-J. (2013) Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein. Journal of Biomedical Science 20, 55.
  35. Huang, F.-L.#, Shiao, Y.-J. #, Hou, S.-J., Yang, C.-N., Chen, Y.-J., Lin, C.-H., Shie, F.-S., Tsay, H.-J. Cysteine-rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Aβ internalization. Journal of Biomedical Science 2013 20, 54. #contribution equally
  36. Lin, Y.-L., Tsay, H.-J., Liao, Y.-F., Wu, M.-F., Wang, C.-N. Shiao, Y.-J. (2012) The components of Flemingia macrophylla attenuates amyloid beta-protein accumulation by regulating amyloid beta-protein metabolic pathway. Evidence-Based Complementary Alternative Medicine 2012, 795843.
  37. Yang, C.-N.#, Shiao, Y.-J. #, Shie, F.-S., Guo, B,-S., Chen, P.-H., Cho, C.-Y., Chen, Y.-J., Huang, F.-L., Tsay, H.-J. (2011) Mechanism mediating oligomeric Aβ clearance by naïve primary microglia. Neurobiology of Dis*contribution equally
  38. Shiao, Y.-J., Chen, W.-P., Kuo, Y.-C., Lin, Y.-L. (2011) Phenylnaphthalenes and dihydronaphthalene deriv atives from the roots of vitex neg undo. Journal of Chinese Medicine 22, 153-159.
  39. Huang, W.-C., Yen, F.-C., Shie, F.-S., Pan, C.-M. Shiao, Y.-J. Yang, C.-N. Huang, F.-L. Sung, Y.-J. Tsay, H.-J. (2010) TGF-beta1 blockade of microglial chemotaxis toward Abeta aggregates involves SMAD signaling and down-regulation of CCL5. Journal of Neuroinflammation 7, 28.
  40. Huang, W.-C., Yen, F.-C., Shiao, Y.-J., Shie F.-S., Chan J.-L., Yang C.-N., Sung Y.-J., Huang F.-L., Tsay H.-J. (2009) Enlargement of Ab aggregates through chemokine-dependent microglial clustering. Neuroscience Research 63(4), 280-287.
  41. Shiao, Y.-J., Chen, W.-P. Lin, Y.-L. (2009) New polyphenols and triterpene from the pseudobulbs of Pleione formosana. Journal of Chinese Chemical Society 56, 828-833.
  42. Chi, C.-W., Lin, Y.-L. Chen, C.-F., Wang C.-N.* and Shiao, Y.-J.* (2008) “Tournefolic acdi B attenuates amyloid b protein mediated toxicity by abrogating the calcium overload in mitochondria and retarding the caspase 8-truncated Bid-cytochrome c pathway in rat cortical neurons” European Journal of Pharmacology 586(1-3), 35-43.
  43. Wang, C.-N., Pan, H.-C., Lin, Y.-L., Chi, C.-W. and Shiao, Y.-J.* (2006) “Ester derivatives of tournefolic acid B attenuate N-Methyl-Daspartate-mediated excitotoxicity in rat cortical neurons” Molecular Pharmacology 69(3), 950-959.
  44. Shiao, Y.-J., Wang, C.-N., Wang, W.-Y., Lin, Y.-L. (2005) Neuroprotective flavonoids from Flemingia macrophylla. Planta Medica 71(9):835-840.
  45. Chi, C.-W., Wang, C.-N., Lin, Y.-L., Chen, C.-F., Shiao, Y.-J. * (2005) Tournefolic acid B methyl ester attenuates glutamate-induced toxicity by blockade of ROS accumulation and abrogating the activation of caspases and JNK in rat cortical neurons. Journal of Neurochemistry 92(3), 692-700.
  46. Shiao, Y.-J., Lin, Y.-L., Sun, Y.-H., Chi, C.-W., Chen, C.-F., Wang, C.-N. (2005) Falcarindiol impairs the expression of inducible nitric oxide synthase by abrogating the activation of IKK and JAK in rat primary astrocytes. British Journal of Pharmacology 144(1), 42-51.
  47. Lin, S.-J. Shiao, Y.-J., Chi, C.-W., Yang, L.-M. (2004) Ab Aggregation Inhibitors. Part 1: Synthesis and Biological Activity of Phenylazo Benzenesulfonamides. Bioorganic & Medicinal Chemistry Letters 14(5), 1173-1176.
  48. Chen, C.-C., Shiao, Y.-J., Lin, R.-D., Shao, Y.-Y., Lai, M.-N. Lin, C.-C., Ng,r, L.-K., Kuo, Y.-H. (2006) “Neuroprotective Diterpenes from the Fruiting Body of Antrodia camphorate. Journal of Natural Products 69(4), 689-691.
  49. Tsai,W.-J., Shiao, Y.-J., Lin, S.-J., Chiou, W.-F., Lin, L.-C., Yang, T.-S., Teng, C.-M., Wu, T.-S., Yang, L.-M. (2006) Selective COX-2 inhibitors. Part 1: Synthesis and biological evaluation of phenylazobenzenesulfonamides. Bioorganic & Medicinal Chemistry Letters 16(17), 4440-4443.
  50. Wang C.-N., Chen, I.-J., Lin Y.-L., Chi, C.-W., Chen, C.-F., Shiao, Y.-J. * (2003) The neuroprotective effects of Uncaria hirsute Haviland on amyloid β protein-induced toxicity in rat cortical neurons. The Chinese Pharmaceutical Journal 55, 319-334.
  51. Shiao, Y.-J., Sun, Y.H., Lin Y.L., Chi, C.W., Chen, C.F., Wang C.N. (2003) “Polyacetyllenes impair the expression of inducuble nitric oxide synthase by abrogating the nuclear translocation of NFkB and Stat1 in rat primary astrocytes” The Chinese Pharmaceutical Journal 55, 391-403.
  52. Lin, Y.-L., Wang, C.-N., Shiao, Y.-J., Liu, T.-Y., Wang, W.-Y. (2003) Benzoligananoid and polyphenols from Origanum vulgare. Journal of Chinese Chemical Sociaty 50, 1079-1083.
  53. Shiao, Y.-J. *, Wang, C.N. (2002) Molecular pathogenesis, treatment strategies and animal models of Alzheimer’s disease. The Chinese Pharmaceutical Journal 54, 1-16.
  54. Wang C.-N., Chi, C.-W., Lin Y.-L., Chen, C.-F. Shiao, Y.-J. * (2001) The neuroprotective effects of phytoestrogens on amyloid β protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. Journal of Biological Chemistry 276(7), 5287-5295.
  55. Lee, T.-F., Shiao, Y.-J., Chen. C.-F., Wang, L.-C.-H. (2001). Effect of ginseng saponins on β-amyloid-suppressed acetylocholine release from rat hippocampal slices. Plnata Madica 67(7), 634-637.
  56. Wang, C.-N., Shiao, Y.-J., Kuo, Y.-H., Chen, C.-C., Lin, Y.-L. (2000) Inducible nitric oxide synthase inhibitor from Saposhnikovae divaricata and Panax quinquefolium. Planta Medica 66(7), 644-647.
  57. Wang, C.-N.#., Shiao, Y.-J. #, Lin, Y.-L., and Chen, C.-F. (1999) Nepalolide A inhibits the expression of inducible nitric oxide synthase by modulating the degradation of IkB-a and IkB-b in c6 glioma cells and rat primary astrocytes. British Journal of Pharmacolology 128(2), 345-356. #Contribution equally.
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