Jung-Yaw Lin

@ntu.edu.tw

Institute of Biochemistry and Molecular Biology
National Taiwan University, College of Medicine

Jung-Yaw Lin


               Download Compact PDF  
https://researchid.co/jylin

RESEARCH INTERESTS

Molecular Biology, Protein Chemistry, Functional Genomics, Biotechnology, Anit-Cancer Drug, and Neuro Protection Drug
161

Scopus Publications

Scopus Publications

  • Puerariae Radix Prevents Anxiety and Cognitive Deficits in Mice under Oligomeric Aβ-Induced Stress
    Hei-Jen Huang, Ching-Yi Huang, Mingchung Lee, Jung-Yaw Lin, Hsiu Mei Hsieh-Li
    American Journal of Chinese Medicine, 2019
    To evaluate the therapeutic effects of Chinese herbal medicine (CHM) for Alzheimer’s disease (AD), we evaluated five CHMs in oligomeric A[Formula: see text]-treated mouse primary hippocampal neuronal cultures. The aqueous extract from the root of Pueraria lobata (Puerariae Radix; PR) showed better neuroprotective effects than did the other four CHM aqueous extracts, including Gardenia jasminoides, Eleutherococcus senticosus, Rhodiola rosea, and Panax, in the primary culture treated with saline or oligomeric A[Formula: see text]. Furthermore, the neuroprotective effects of aqueous extract of PR were also better than its well-known active compound, puerarin, against the neurotoxicity of oligomeric A[Formula: see text] in a primary culture. For in vivo experiments, C57BL/6J male mice that received direct infusion of soluble oligomeric A[Formula: see text] into the bilateral hippocampal CA1 subregion were used as an alternative AD mouse model. The effects and molecular mechanisms of chronic systemic administration of PR aqueous extract were evaluated in the alternative AD model. PR aqueous extract prevented anxiety and cognitive impairment in mice associated with a decrease in the levels of A[Formula: see text] deposition, tau protein phosphorylation, inflammation, loss of noradrenergic, and serotonergic neurons and an increase in the levels of synaptophysin and insulin degrading enzyme (IDE) against the toxicity of oligomeric A[Formula: see text]. Furthermore, no obvious damage to the liver and kidney was detected after chronic systemic administration of PR aqueous extract. Therefore, using PR could be a safer, more effective therapeutic strategy than using its active compound puerarin to prevent both cognitive and noncognitive dysfunction and related pathological features of AD.
  • Targeting Ubiquitin Proteasome Pathway with Traditional Chinese Medicine for Treatment of Spinocerebellar Ataxia Type 3
    I-Cheng Chen, Chia-Ning Chang, Wan-Ling Chen, Te-Hsien Lin, Chih-Ying Chao, et al.
    American Journal of Chinese Medicine, 2019
    Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q[Formula: see text]-GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q[Formula: see text]-GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.
  • Aqueous extracts of Paeonia suffruticosa modulates mitochondrial proteostasis by reactive oxygen species-induced endoplasmic reticulum stress in pancreatic cancer cells
    Yu-Huei Liu, Yui-Ping Weng, Hsin-Ying Tsai, Chao-Jung Chen, Der-Yen Lee, et al.
    Phytomedicine, 2018
  • Chinese Herbal Medicine Glycyrrhiza inflata Reduces Aβ Aggregation and Exerts Neuroprotection through Anti-Oxidation and Anti-Inflammation
    Ya-Jen Chiu, Chi-Mei Lee, Te-Hsien Lin, Hsuan-Yuan Lin, Shin-Ying Lee, et al.
    American Journal of Chinese Medicine, 2018
    Amyloid [Formula: see text] (A[Formula: see text]) plays a major role in the pathogenesis of Alzheimer’s disease (AD). The accumulation of misfolded A[Formula: see text] causes oxidative and inflammatory damage leading to apoptotic cell death. Chinese herbal medicine (CHM) has been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of CHM extract Glycyrrhiza inflata (G. inflata) and its active constituents, licochalcone A and liquiritigenin in AD. We examined A[Formula: see text] aggregation inhibition, anti-oxidation and neuroprotection in Tet-On A[Formula: see text]-GFP 293/SH-SY5Y cells and anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 and LPS and interferon (IFN)-[Formula: see text] (LPS/IFN-[Formula: see text])-activated BV-2 cells. In addition, we applied conditioned media (CM) of BV-2 cells primed with LPS/IFN-[Formula: see text] to A[Formula: see text]-GFP SH-SY5Y cells to uncover the neuroprotective mechanisms. Our results showed that G. inflata extract and its two constituents displayed potentials of A[Formula: see text] aggregation inhibition and radical-scavenging in biochemical assays, A[Formula: see text] misfolding inhibition and reactive oxygen species (ROS) reduction in A[Formula: see text]-GFP 293 cells, as well as neurite outgrowth promotion, acetylcholinesterase inhibition and SOD2 up-regulation in A[Formula: see text]-GFP SH-SY5Y cells. Meanwhile, both G. inflata extract and its constituents suppressed NO, TNF-[Formula: see text], IL-1[Formula: see text], PGE2 and/or Iba1 productions in inflammation-stimulated RAW 264.7 or BV-2 cells. G. inflata extract and its constituents further protected A[Formula: see text]-GFP SH-SY5Y cells from BV-2 CM-induced cell death by ameliorating reduced BCL2 and attenuating increased IGFBP2, cleaved CASP3, BAD and BAX. Collectively, G. inflata extract, licochalcone A and liquiritigenin display neuroprotection through exerting anti-oxidative and anti-inflammatory activities to suppress neuronal apoptosis.
  • Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome
    Tsung-Wei Su, Chao-Yu Yang, Wen-Pin Kao, Bai-Jiun Kuo, Shan-Meng Lin, et al.
    Structure, 2017
  • Aqueous extract of Polygonum bistorta modulates proteostasis by ROS-induced ER stress in human hepatoma cells
    Yu-Huei Liu, Yui-Ping Weng, Hsuan-Yuan Lin, Sai-Wen Tang, Chao-Jung Chen, et al.
    Scientific Reports, 2017
    Hepatocellular carcinoma (HCC) remains the leading cause of cancer mortality with limited therapeutic targets. The endoplasmic reticulum (ER) plays a pivotal role in maintaining proteostasis in normal cells. However, alterations in proteostasis are often found in cancer cells, making it a potential target for therapy. Polygonum bistorta is used in traditional Chinese medicine owing to its anticancer activities, but the molecular and pharmacological mechanisms remain unclear. Using hepatoma cells as a model system, this study demonstrated that P. bistorta aqueous extract (PB) stimulated ER stress by increasing autophagosomes but by blocking degradation, followed by the accumulation of ubiquitinated proteins and cell apoptosis. In addition, an autophagy inhibitor did not enhance ubiquitinated protein accumulation whereas a reactive oxygen species (ROS) scavenger diminished both ubiquitinated protein accumulation and ligand-stimulated epidermal growth factor receptor (EGFR) expression, suggesting that ROS generation by PB may be upstream of PB-triggered cell death. Nevertheless, PB-exerted proteostasis impairment resulted in cytoskeletal changes, impairment of cell adhesion and motility, and inhibition of cell cycle progression. Oral administration of PB delayed tumour growth in a xenograft model without significant body weight loss. These findings indicate that PB may be a potential new alternative or complementary medicine for HCC.
  • Protective Effects of Wogonin against Alzheimer's Disease by Inhibition of Amyloidogenic Pathway
    Ding-Siang Huang, Yu-Chen Yu, Chung-Hsin Wu, Jung-Yaw Lin
    Evidence Based Complementary and Alternative Medicine, 2017
    One of the pathogenic systems of Alzheimer’s disease (AD) is the formation ofβ-amyloid plaques in the brains of patients, and amyloidogenic activity becomes one of the therapeutic targets. Here, we report wogonin, one of the major active constituting components inScutellaria baicalensis, which has the neuroprotective effects on amyloid-βpeptides- (Aβ-) induced toxicity. Oral wogonin treatment improved the performance of triple transgenic AD mice (h-APPswe, h-Tau P301L, and h-PS1 M146V) on the Morris water maze, Y-maze, and novel object recognition. Furthermore, wogonin activated the neurite outgrowth of AD cells by increasing neurite length and complexity of Tet-On Aβ42-GFP SH-SY5Y neuroblastoma cells (AD cells) and attenuated amyloidogenic pathway by decreasing the levels ofβ-secretase, APPβ-C-terminal fragment, Aβ-aggregation, and phosphorylated Tau. Wogonin also increased mitochondrial membrane potential (∆ψm) and protected against apoptosis by reducing the expression of Bax and cleaved PARP. Collectively, these results conclude that wogonin may be a promising multifunctional drug candidate for AD.
  • The aqueous extract of Glycyrrhiza inflata can upregulate unfolded protein response-mediated chaperones to reduce tau misfolding in cell models of Alzheimer’s disease
    Guey-Jen Lee-Chen, Kuo-Hsuan Chang, I-Cheng Chen, Husan-Yuan Lin, Hsuan-Chiang Chen, et al.
    Drug Design Development and Therapy, 2016
    Background Alzheimer’s disease (AD) and several neurodegenerative disorders known as tauopathies are characterized by misfolding and aggregation of tau protein. Although several studies have suggested the potential of traditional Chinese medicine (TCM) as treatment for neurodegenerative diseases, the role of TCM in treating AD and tauopathies have not been well explored. Materials and methods Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of repeat domain of tau (ΔK280 tauRD) with DsRed. The ΔK280 tauRD-DsRed fusion gene was then used to generate Tet-On 293 and SH-SY5Y cell clones as platforms to test the efficacy of 39 aqueous extracts of TCM in reducing tau misfolding and in neuroprotection. Results Seven TCM extracts demonstrated a significant reduction in tau misfolding and reactive oxidative species with low cytotoxicity in the ΔK280 tauRD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ΔK280 tauRD-DsRed SH-SY5Y neuronal cell model. G. inflata further rescued the upregulation of ERN2 (pro-apoptotic) and downregulation of unfolded-protein-response-mediated chaperones ERP44, DNAJC3, and SERP1 in ΔK280 tauRD-DsRed 293 cells. Conclusion This in vitro study provides evidence that G. inflata may be a novel therapeutic for AD and tauopathies. Future applications of G. inflata on animal models of AD and tauopathies are warranted to corroborate its effect of reducing misfolding and potential disease modification.
  • Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17
    Chung-Hsin Wu, Ding-Siang Huang, Husan-Yuan Lin, Guey-Jen Lee-Chen, Hsiu-Mei Hsieh, et al.
    Drug Design Development and Therapy, 2016
    Spinocerebellar ataxia type 17 (SCA 17) is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP) gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day) could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.
  • The potential of synthetic indolylquinoline derivatives for Aβ aggregation reduction by chemical chaperone activity
    Kuo-Hsuan Chang, Ya-Jen Chiu, Shu-Ling Chen, Chen-Hsiang Huang, Chih-Hsin Lin, et al.
    Neuropharmacology, 2016
  • Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma
    Chung-Yu Ku, Yu-Huei Liu, Hsuan-Yuan Lin, Shao-Chun Lu, Jung-Yaw Lin
    Oncotarget, 2016
  • Corosolic acid inhibits hepatocellular carcinoma cell migration by targeting the VEGFR2/Src/FAK pathway
    Chung-Yu Ku, Ying-Ren Wang, Hsuan-Yuan Lin, Shao-Chun Lu, Jung-Yaw Lin
    Plos One, 2015
  • The potential of lactulose and melibiose, two novel trehalase-indigestible and autophagy-inducing disaccharides, for polyQ-mediated neurodegenerative disease treatment
    Guan-Chiun Lee, Chih-Hsin Lin, Yu-Chen Tao, Jinn-Moon Yang, Kai-Cheng Hsu, et al.
    Neurotoxicology, 2015
  • Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models
    Guey-Jen Lee-Chen, Pin-Jui Kung, Yu-Chen Tao, Ho-Chiang Hsu, Donala Janreddy, et al.
    Drug Design Development and Therapy, 2014
  • Aqueous extract of Gardenia jasminoides targeting oxidative stress to reduce polyQ aggregation in cell models of spinocerebellar ataxia 3
    Kuo-Hsuan Chang, Wan-Ling Chen, Yih-Ru Wu, Te-Hsien Lin, Yi-Ci Wu, et al.
    Neuropharmacology, 2014
  • Aqueous extract of Glycyrrhiza inflata inhibits aggregation by upregulating PPARGC1A and NFE2L2-ARE pathways in cell models of spinocerebellar ataxia 3
    Chiung-Mei Chen, Yu-Ting Weng, Wan-Ling Chen, Te-Hsien Lin, Chih-Ying Chao, et al.
    Free Radical Biology and Medicine, 2014
  • Yang-Dan-Tang, identified from 15 Chinese herbal formulae, inhibits human lung cancer cell proliferation via cell cycle arrest
    Tien-Chun Wang, Chih-Nan Fang, Chih-Chien Shen, Hui-Yu Wei, Yui-Ping Weng, et al.
    Evidence Based Complementary and Alternative Medicine, 2012
  • Full-length enrich c-DNA libraries-clear cell-renal cell carcinoma
    Sai-Wen Tang, Jung-Yaw Lin
    Journal of Oncology, 2012
  • Role of the CCAAT-binding protein NFY in SCA17 pathogenesis
    Li-Ching Lee, Chiung-Mei Chen, Hao-Chun Wang, Hsiao-Han Hsieh, I-Sheng Chiu, et al.
    Plos One, 2012
  • Aqueous extract of Paeonia suffruticosa inhibits migration and metastasis of renal cell carcinoma cells via suppressing VEGFR-3 pathway
    Shih-Chin Wang, Sai-Wen Tang, Sio-Hong Lam, Chung-Chieh Wang, Yu-Huei Liu, et al.
    Evidence Based Complementary and Alternative Medicine, 2012
  • Effects of a Chinese herbal medicine, Guan-Jen-Huang (Aeginetia indica Linn.), on renal cancer cell growth and metastasis
    Yu-Huei Liu, Meng-Luen Li, Meng-Yu Hsu, Ya-Yueh Pang, I-Ling Chen, et al.
    Evidence Based Complementary and Alternative Medicine, 2012
  • Involvement of prohibitin upregulation in abrin-triggered apoptosis
    Yu-Huei Liu, Konan Peck, Jung-Yaw Lin
    Evidence Based Complementary and Alternative Medicine, 2012
  • Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells
    Sai-Wen Tang, Tsung-Cheng Yang, Wei-Chou Lin, Wen-Hsin Chang, Chung-Chieh Wang, et al.
    Carcinogenesis, 2011
  • Recognition intensities of submolecular structures, mammalian glyco-structural units, ligand cluster and polyvalency in abrin-a-carbohydrate interactions
    June H. Wu, Albert M. Wu, Zhangung Yang, Yuen-Yuen Chen, Biswajit Singha, et al.
    Biochimie, 2010
  • A biophysical elucidation for less toxicity of Agglutinin than Abrin-a from the seeds of Abrus Precatorius in consequence of crystal structure
    Jack Cheng, Tian-Huey Lu, Chao-Lin Liu, Jung-Yaw Lin
    Journal of Biomedical Science, 2010