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Hey-Jen Tsay Professor

Laborataory of Neural Development and Regeneration

Hey-Jen Tsay Professor



Ph.D., Dept. Biochemistry
New York State University at Stony Brook


Research Interest

Our research interest is focused on the role of microglia at the late stage and early stage of Alzheimer’s disease (AD).  At the late stage, overactivated microglia clustering at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in AD.  Therefore, attenuating microglia clustering can reduce the focal neuroinflammation at neuritic plaques.  We have identified CCL5 and CCL2 as prominent chemokines mediating the chemotactic migration of microglia toward Abeta aggregates. We find that TGF-beta1 reduces Abeta-induced microglial chemotaxis through the SMAD2 pathway.  The down-regulation of CCL5 by TGF-beta1, at least, partially contributes to the clustering of microglia at Abeta aggregates.  TGF-beta1 may ameliorate microglia-mediated neuroinflammation in AD by preventing activated microglia clustering at neuritic plaques.

At the early stage, the accumulation of soluble oligomeric amyloid-beta peptide prior to the presence of senile plaques contributes to synaptic and memory deficits in AD. Although microglia are prominent on oAbeta uptake in CNS, the mechanism of mediating microglial oAbeta clearance remains unclear.  Our study suggests that scavenger receptor at the plasma membrane and lysosomal capthesin B are critical for microglial oAbeta clearance.  This study provides the first insight into how microglia are involved in the clearance of oAbeta and their roles at the early stages of AD.

More than 95% of AD are sporadic without familial history.  During the aging process, vesicular damages are associated with sporadic AD.  Our recent project is focused on establishing stroke animal models and ask the impact of vesicular damages on the initiation of AD . 


Invited Lectures/Publications

高脂飼料機制性的結果published in International Journal of Molecular Sciences (Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation). 及高蔗糖飼料機制性的結果published in Neurobiology of Aging, 2019 (A high-sucrose diet aggravates Alzheimer's disease's pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice).

Han-Min Chen, Lin-Chien Lee, Kuang-Yu Hu, Wei-Jern Tsai, Cheng Huang, Huey-Jen Tsay, Hui-Kang Liu*IThe application of post-translational modification oriented serum proteomics to assess experimental diabetes with complications. PlosOne (2018):e 0206509.

Yi-Heng Lee† Hao-Chieh Hsu †, Pei-Chen Kao , Young-Ji Shiao , Skye Hsin-Hsien Yeh, Feng-Shiun Shie Shu-Meng Hsu, Chih-Wen Yeh ,Hui-Kang Liu 4,9, Shi-Bing Yang,*and Huey-Jen TsayAugmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation. International Journal of Molecular Sciences 19 (2018) 2333. 

Tsai-Teng Tzeng, Chien-Chih Chen, Chin-Chu Chen, Huey-Jen Tsay , Li-Ya Lee, Wan-Ping Chen, Chien-Chang Shenand Young-Ji Shiao 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 (2018) 598.

Yung-Cheng Huang†, Huey-Jen Tsay†, Mei-Kuang Lu , Chien-Hung Lin , Chih-Wen Yeh , Hui-Kang Liu* and Young-Ji Shiao* Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice. International Journal of Molecular Sciences. 18 (2017) 2746 

Chih-Wen Yeha, Hui-Kang Liub,c, Lie-Chwen Linb, Kou-Tong Lioud, Yung-Cheng Huange, Chien-Hung Lina, Tsai-Teng Tzengf, Feng-Shiun Shieg, Huey-Jen Tsay*, Young-Ji Shiao* (2017) Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice. Journal of Ethnopharmacology 209 (2017) 50–61

Chang CC†, Yuan W†, Lin YL, Liu RS, Juan YC, Sun WH,6 Tsay HJ , Huang HC, Lee YC, and Liu HK (2016) Evaluation of the In Vivo therapeutic effects of Radix Paeoniae Rubra Ethanol Extract with the hypoglycemic activities Measured from multiple cell-based assays. Evidence-Based Complementary and Alternative Medicine 25(1):123

Chang CC, Yuan W, Roan HY, Chang JL, Huang HC, Lee YC, Tsay HJ and Liu HK (2016) The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity. Complementary and Alternative Medicine 16(1): 432

 Lee KI, Lee HT, Lin HC, Tsay HJ, Tsai C, Shyue SK, Lee TS (2016) The Role of transient receptor potential ankyrin 1 channels in Alzheimer’s disease.J Neuroinflammation 13(1): 92.

Tsay HJ, Huang YC†, Chen YJ, Lee YH, Hsu SM, Tsai KC, Yang CN, Huang FL, Shie FS, Lee LC, Shiao YJ (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. J. Biomedical Sci. 23:27

Shie FS, Shiao YJ, Yeh CW, Lin CH, Tzeng TT, Hsu HC, Huang FL, Tsay HJ*, Liu HK* (2015) Obesity and hepatic steatosis are associated with elevated serum amyloid beta in metabolically stressed APPswe/PS1dE9 Mice. Plos One 10(8):e0134531

Yeh CW, Skye Yeh HH, Shie FS, Lai WS, Liu HK , Tzeng TT, Tsay HJ *, and Shiao YJ *(2015) Aggravated cognitive dysfunction and impaired cerebral glucose regulation are associated with astrocytic activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice. Neurobiology of Aging 2015 36(11): 2984-94. 

Lin YL †, Tsay HJ †, Lai TH, Tzeng TT and Shiao YJ * Lithospermic acid attenuates1-methyl-4-phenylpyridine -induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways. J. Biomedical Sci. 22:37.

Tzeng TT, Tsay HJ , Chang L, Hsu CL, Lai TH, Huang FL, and Shiao YJ* (2014) Caspase 3 involves in neuroplasticity, microglial activation, and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid. J. Biomedical Sci. 20:9

Tsay HJ , Huang YC, Huang FL, Chen CP, Tsai YH, Wang YH, Wu MF, Chiang FY, and Shiao YJ* (2013) Amyloid beta peptide-mediated neurotoxicity is attenuated by the proliferating microglia more potently than by the quiescent phenotype. J. Biomedical Sci. 20:78.

Liu YH, Lai WS, Tsay HJ*, Wang TW* and Yu JY* (2013) Effects of prenatal immune activation on adult neurogenesis in the subventricular zone-olfactory bulb pathway and odor discrimination. Schizophrenia Research 151, 1–11.

Huang FL, Shiao YJ, Hou SJ, Yang CN, Chen YJ, Lin CH, Shie FS, Tsay HJ* (2013) Cysteine-Rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Ab internalization. J. Biomedical Sci. 20:54. 

Wang CJ, Chen CC, Tsay HJ, Chiang  FY , Wu MF , Shiao YJ* (2013) Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein. J. Biomedical Sci. 20:53. 

 Lin YL, Tsay HJ , Liao YF, Wu MF, Wang CN, and Shiao YJ* (2012) The components of Flemingia macrophylla attenuates amyloid beta-protein accumulation by regulating amyloid beta-protein metabolic pathway. Evid. based Complement. Alternat. Med. 795843.

Yang DC, Tsai CC, Liao YF, Fu HC, Tsay HJ, TF Huang, Chen YH *, Hung SC. (2012) Twist Controls Skeletal Development and Dorsoventral Patterning by Regulating Runx2 in Zebrafish. Plos One

Wang CC, Huang HB , Tsay HJ  , Shiao MS, Wu WJ, Cheng YC , Lin TH (2012) Characterization of Aβ aggregation mechanism probed by congo red J Biomol Struct Dyn. 30(2):160-9 

Yang CN, Shiao YJ, Shie FS, Guo BS, Chen PH, Chou CY, Chen YJ, Huang FL, and Tsay HJ: Mechanism mediating oligomeric Abeta clearance by naive primary microglia . Neurobiology of Disease 2011.
Huang YC, Chen YC, Tsay HJ, Chyan CL, Chen CY, Huang HB, and Lin TH: The effect of PKA-phosphorylation on the structure of inhibitor-1 studied by NMR spectroscopy. J. Biochem. 147:273-278, 2010.
Chen JH, Hsu PC, Wang LW, Tsay HJ, Kan IJ, and Shie FS: Modulation of microglial immune response by a novel thiourea derivative. Chem Biol Interact 2010.
Huang WC, Yen FC, Shie FS, Pan CM, Shiao YJ, Yang CN, Huang FL, Sung YJ, and Tsay HJ: TGF-beta1 blockade of microglial chemotaxis toward Amyloid-beta aggregrates involves SMAD signaling and down-regulation of CCL5. J. Neuroinflammation 7:28-38,2010.
Huang WC, Yen FC, Shiao YJ , Chan JL, Shie FS, Yang CN, Sung YJ, Huang FL, and Tsay HJ: Enlargement of Amyloid-beta aggregates through chemokine-dependent microglia clustering. Neuroscience Research 63:280-287, 2009.
Wu SH, Chen YH, Huang F-L, Chang CH, Chang YF, Tsay HJ: Multiple Regulatory Elements Mediating Neuronal-Specific Expression of Zebrafish Sodium Channel Gene, Scn8aa. Dev. Dyn. 237: 2554-2565, 2008.
Yang DC, Tsay HJ, Lin SY, Chiou SH, Li MJ, Chang TJ, and Hung SC: cAMP/PKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKL/OPG mRNA Expression in Mesenchymal Stem Cells by Suppressing Leptin. Plos one 3 (2)1540-1550, 2008.
Chen YH, Huang YH, Wang YH, and Tsay HJ: Teratogenic Effects of Caffeine on Zebrafish. Neurotoxicology and Teratology 30:440-447, 2008.
Wang YH, Li CK, Lee GH, Tsay HJ, Tsai HJ, and Chen YH: Inactivation of Zebrafish mrf4 Leads to Myofibril Misalignment and Motor Axon Growth Disorganization. Dev. Dyn. 237: 1043-1050, 2008.
Chen YH, Huang FL, Cheng YC, Wu CJ, and Tsay HJ: Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities. J. Biomedical Sci. 15: 69-78, 2008.