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Article: MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish.

Lai, Chi-Yu / Yeh, Kun-Yun / Liu, Bi-Feng / Chang, Tzu-Ming / Chang, Chuan-Hsun / Liao, Yung-Feng / Liu, Yi-Wen / Her, Guor Mour

Cancers

2021 Volume 13, Issue 21

Abstract: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, ... ...

Abstract	Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.
Language	English
Publishing date	2021-11-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13215565
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Article ; Online: Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases.

Bhore, Noopur / Wang, Bo-Jeng / Chen, Yun-Wen / Liao, Yung-Feng

International journal of molecular sciences

2017 Volume 18, Issue 9

Abstract: Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and ... ...

Abstract	Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and stressful conditions. The role of the PN in neurodegenerative disease is well-documented, where it is known to respond to changes in protein folding states or toxic gain-of-function protein aggregation. Dual-specificity phosphatases have recently emerged as important participants in maintaining balance within the PN, acting through modulation of cellular signaling pathways that are involved in neurodegeneration. In this review, we will summarize recent findings describing the roles of dual-specificity phosphatases in neurodegeneration and offer perspectives on future therapeutic directions.
Language	English
Publishing date	2017-09-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18091963
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Article ; Online: New Hydroxyquinoline-Based Derivatives as Potent Modulators of Amyloid-β Aggregations.

Fu, Chin-Lan / Hsu, Li-Shin / Liao, Yung-Feng / Hu, Ming-Kuan

Archiv der Pharmazie

2016 Volume 349, Issue 5, Page(s) 327–341

Abstract: Copper and zinc have been found to contribute to the burden of amyloid-β (Aβ) aggregations in neurodegenerative Alzheimer's disease (AD). Dysregulation of these metals leads to the generation of reactive oxygen species (ROS) and eventually results in ... ...

Abstract	Copper and zinc have been found to contribute to the burden of amyloid-β (Aβ) aggregations in neurodegenerative Alzheimer's disease (AD). Dysregulation of these metals leads to the generation of reactive oxygen species (ROS) and eventually results in oxidative damage and accumulation of the Aβ peptide, which are the key elements of the disease. Aiming to pursue the discovery of new modulators for the disease, we here rationally focused on conjugating the core hydroxyquinoline of the metal-protein attenuating compound PBT2 and the N-methylanilide analogous moiety of the Aβ imaging agent to build a new type of multi-target modulators of Aβ aggregations. We found that the N,N-dimethylanilinyl imines 7a, 8a, and the corresponding amines 7b, 8b exerted efficient inhibition of Cu(2+) - or Zn(2+) -induced Aβ aggregations and significant disassembly of metal-mediated Aβ aggregated fibrils. Further, 7a and 7b also exhibited significant ROC scavenging effects compared to PBT2. The results suggested that 7a and 7b are promising lead compounds for the development of a new therapy for AD.
MeSH term(s)	Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/drug effects ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Peptides/ultrastructure ; Chelating Agents/chemical synthesis ; Chelating Agents/pharmacology ; Chelating Agents/therapeutic use ; Clioquinol/analogs & derivatives ; Clioquinol/chemistry ; Clioquinol/pharmacology ; Clioquinol/therapeutic use ; Copper/adverse effects ; Hydroxyquinolines/chemical synthesis ; Hydroxyquinolines/chemistry ; Hydroxyquinolines/pharmacology ; Hydroxyquinolines/therapeutic use ; Protein Aggregation, Pathological/drug therapy ; Structure-Activity Relationship ; Zinc/adverse effects
Chemical Substances	Amyloid beta-Peptides ; Chelating Agents ; Hydroxyquinolines ; PBT2 compound ; Copper (789U1901C5) ; Clioquinol (7BHQ856EJ5) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2016-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6381-2
ISSN	1521-4184 ; 0365-6233 ; 1437-1014
ISSN (online)	1521-4184
ISSN	0365-6233 ; 1437-1014
DOI	10.1002/ardp.201500453
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Article ; Online: Calreticulin regulates MYCN expression to control neuronal differentiation and stemness of neuroblastoma.

Lee, Andy Chi-Lung / Shih, Yu-Yin / Zhou, Fanfan / Chao, Tsi-Chian / Lee, Hsinyu / Liao, Yung-Feng / Hsu, Wen-Ming / Hong, Ji-Hong

Journal of molecular medicine (Berlin, Germany)

2019 Volume 97, Issue 3, Page(s) 325–339

Abstract: Oncogenic N-MYC (MYCN) is widely used as a biomarker in clinics for neuroblastoma (NB) patients; nevertheless, mechanism that underlines MYCN regulation remains elusive. In the present study, we identified calreticulin (CRT) as a novel MYCN suppressor ... ...

Abstract	Oncogenic N-MYC (MYCN) is widely used as a biomarker in clinics for neuroblastoma (NB) patients; nevertheless, mechanism that underlines MYCN regulation remains elusive. In the present study, we identified calreticulin (CRT) as a novel MYCN suppressor that downregulated MYCN promoter activity and protein expression to modulate neuronal differentiation and stemness. Our data showed that CRT-mediated MYCN suppression led to increased neurite length and commensurate elevation in differentiation marker GAP-43. We examined effect of radiotherapy and discovered that ionizing radiation (IR) was able to augment CRT expression dose-dependently in NB. Interestingly, neuronal differentiation and neurosphere formation (NSF) of NB were not only co-modulated by IR and CRT but were also dependent on Ca
MeSH term(s)	Animals ; Calreticulin/metabolism ; Cell Line, Tumor ; Female ; Humans ; Mice, SCID ; N-Myc Proto-Oncogene Protein/genetics ; N-Myc Proto-Oncogene Protein/metabolism ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Neuroblastoma/radiotherapy ; Neurogenesis ; Neurons/physiology ; Promoter Regions, Genetic ; Radiation, Ionizing
Chemical Substances	CALR protein, human ; Calreticulin ; MYCN protein, human ; N-Myc Proto-Oncogene Protein
Language	English
Publishing date	2019-01-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-018-1730-x
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Article ; Online: Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein.

Bhore, Noopur / Wang, Bo-Jeng / Wu, Po-Fan / Lee, Yen-Lurk / Chen, Yun-Wen / Hsu, Wen-Ming / Lee, Hsinyu / Huang, Yi-Shuian / Yang, Ding-I / Liao, Yung-Feng

Molecular neurobiology

2021 Volume 58, Issue 5, Page(s) 2204–2214

Abstract: Dual-specificity phosphatases (DUSPs) comprise a unique group of enzymes that dephosphorylate signaling proteins at both phospho-serine/threonine and phospho-tyrosine residues. Since Notch signaling is an essential pathway for neuronal cell fate ... ...

Abstract	Dual-specificity phosphatases (DUSPs) comprise a unique group of enzymes that dephosphorylate signaling proteins at both phospho-serine/threonine and phospho-tyrosine residues. Since Notch signaling is an essential pathway for neuronal cell fate determination and development that is also upregulated in Alzheimer's disease tissues, we sought to explore whether and how DUSPs may impact Notch processing. Our results show that overexpression of DUSP15 concomitantly and dose-dependently increased the steady-state levels of recombinant Notch (extracellular domain-truncated Notch, NotchΔE) protein and its cleaved product, Notch intracellular domain (NICD). The overall ratio of NotchΔE to NICD was unchanged by overexpression of DUSP15, suggesting that the effect is independent of γ-secretase. Interestingly, overexpression of DUSP15 also dose-dependently increased phosphorylated ERK1/2. Phosphorylated ERK1/2 is known to be positively correlated with Notch protein level, and we found that DUSP15-mediated regulation of Notch was dependent on ERK1/2 activity. Together, our findings reveal the existence of a previously unidentified DUSP15-ERK1/2-Notch signaling axis, which could potentially play a role in neuronal differentiation and neurological disease.
MeSH term(s)	Amyloid Precursor Protein Secretases/metabolism ; Cell Differentiation/physiology ; Dual-Specificity Phosphatases/metabolism ; HEK293 Cells ; Humans ; Neurons/metabolism ; Phosphorylation ; Receptors, Notch/metabolism ; Signal Transduction/physiology
Chemical Substances	Receptors, Notch ; DUSP15 protein, human (EC 3.1.3.48) ; Dual-Specificity Phosphatases (EC 3.1.3.48) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-020-02254-0
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Zs.A 2411: Show issues

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Article ; Online: Difluorophenylglycinols as new modulators of proteolytic processing of amyloid precursor proteins.

Chen, Chia-Yu / Liao, Yung-Feng / Chang, Ming-Yun / Hu, Ming-Kuan

Archiv der Pharmazie

2014 Volume 347, Issue 3, Page(s) 161–173

Abstract: Synthesis and evaluation of difluorophenylglycinols as new modulators of proteolytic processing of the amyloid-β precursor proteins for Alzheimer's therapies were described. A range of N-substituted (R)- and (S)-difluorophenylglycinols, structured on the ...

Abstract	Synthesis and evaluation of difluorophenylglycinols as new modulators of proteolytic processing of the amyloid-β precursor proteins for Alzheimer's therapies were described. A range of N-substituted (R)- and (S)-difluorophenylglycinols, structured on the amino alcohol framework, were explored by incorporating the arylsulfonyl moieties and various N-substituents. Evans' chiral auxiliary strategy was employed for the asymmetric synthesis of these enantiomeric difluorophenylglycinols. Compounds with effects on the γ-secretase inhibition and ERK-mediated signaling pathways were evaluated on cell-based assays. Among them, N-cyclopropylmethyl derivatives R-12c and R-13c showed modest γ-secretase inhibition as well as ERK-dependent activation.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/enzymology ; Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Amyloid Precursor Protein Secretases/genetics ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Enzyme Activation ; Ethanolamines/chemical synthesis ; Ethanolamines/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; HEK293 Cells ; Humans ; Molecular Structure ; Protease Inhibitors/chemical synthesis ; Protease Inhibitors/pharmacology ; Proteolysis ; Signal Transduction/drug effects ; Structure-Activity Relationship ; Transfection
Chemical Substances	Amyloid beta-Protein Precursor ; Ethanolamines ; Protease Inhibitors ; N-phenylethanolamine (630DL2N96B) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2014-03
Publishing country	Germany
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6381-2
ISSN	1521-4184 ; 0365-6233 ; 1437-1014
ISSN (online)	1521-4184
ISSN	0365-6233 ; 1437-1014
DOI	10.1002/ardp.201300283
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Article ; Online: Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms.

Wang, Bo-Jeng / Wu, Pei-Yi / Chen, Yun-Wen / Chang, Yu-Tzu / Bhore, Noopur / Wu, Po-Fan / Liao, Yung-Feng

Journal of visualized experiments : JoVE

2018 , Issue 131

Abstract: We have developed a pair of cell-based reporter gene assays to quantitatively measure γ-secretase cleavage of distinct substrates. This manuscript describes procedures that may be used to monitor γ-secretase-mediated cleavage of either APP-C99 or Notch, ... ...

Abstract	We have developed a pair of cell-based reporter gene assays to quantitatively measure γ-secretase cleavage of distinct substrates. This manuscript describes procedures that may be used to monitor γ-secretase-mediated cleavage of either APP-C99 or Notch, using a Gal4 promoter-driven firefly luciferase reporter system. These assays were established by stably co-transfecting HEK293 cells with the Gal4-driven luciferase reporter gene and either the Gal4/VP16-tagged C-terminal fragment of APP (APP-C99; CG cells), or the Gal4/VP16-tagged Notch-ΔE (NΔE; NG cells). Using these reporter assays in parallel, we have demonstrated that an ErbB2 inhibitor, CL-387,785, can preferentially suppress γ-secretase cleavage of APP-C99 in CG cells, but not NΔE in NG cells. The differential responses exhibited by the CG and NG cells, when treated with CL-387,785, represent a preferred characteristic for γ-secretase modulators, and these responses are in stark contrast to the pan-inhibition of γ-secretase induced by DAPT. Our studies provide direct evidence that γ-secretase activities toward different substrates can be differentiated in a cellular context. These new assays may therefore be useful tools in drug discovery for improved AD therapies.
MeSH term(s)	Amyloid Precursor Protein Secretases/analysis ; Amyloid Precursor Protein Secretases/metabolism ; Cell Differentiation/physiology ; HEK293 Cells ; Humans ; Luciferases, Firefly/chemistry ; Luciferases, Firefly/metabolism ; Receptors, Notch/metabolism ; Substrate Specificity ; Transfection
Chemical Substances	Receptors, Notch ; Luciferases, Firefly (EC 1.13.12.7) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2018-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/56795
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Article ; Online: Phosphatidylinositol-4-phosphate 5-kinase type 1α attenuates Aβ production by promoting non-amyloidogenic processing of amyloid precursor protein.

Wu, Po-Fan / Bhore, Noopur / Lee, Yen-Lurk / Chou, Ju-Yun / Chen, Yun-Wen / Wu, Pei-Yi / Hsu, Wen-Ming / Lee, Hsinyu / Huang, Yi-Shuian / Lu, Pei-Jung / Liao, Yung-Feng

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2020 Volume 34, Issue 9, Page(s) 12127–12146

Abstract: Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-β peptide (Aβ). The production of Aβ is mediated by sequential proteolysis of amyloid precursor protein ( ...

Abstract	Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-β peptide (Aβ). The production of Aβ is mediated by sequential proteolysis of amyloid precursor protein (APP) by β- and γ-secretases, and has been implicated as the essential determinant of AD pathology. Previous studies have demonstrated that the level of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in the membrane may potentially modulate Aβ production. Given that PI(4,5)P2 is produced by type 1 phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), we sought to determine whether the level of PIP5K type Iα (PIP5K1A) can affect production of Aβ by modulating the lipid composition of the membrane. Using a HEK-derived cell line that constitutively expresses yellow fluorescent protein-tagged APP (APP-YFP), we demonstrated that overexpression of PIP5K1A results in significant enhancement of non-amyloidogenic APP processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted Aβ. Consistently, cells overexpressing PIP5K1A exhibited a significant redistribution of APP-YFP from endosomal compartments to the cell surface. Our findings suggest that PIP5K1A may play a critical role in governing Aβ production by modulating membrane distribution of APP, and as such, the pathway may be a valuable therapeutic target for AD.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; HEK293 Cells ; Humans ; Phosphatidylinositol 4,5-Diphosphate/genetics ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Rats
Chemical Substances	Amyloid beta-Peptides ; Phosphatidylinositol 4,5-Diphosphate ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; 1-phosphatidylinositol-4-phosphate 5-kinase (EC 2.7.1.68)
Language	English
Publishing date	2020-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202000113R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Equilibrative nucleoside transporter 1 inhibition rescues energy dysfunction and pathology in a model of tauopathy.

Chang, Ching-Pang / Chang, Ya-Gin / Chuang, Pei-Yun / Nguyen, Thi Ngoc Anh / Wu, Kuo-Chen / Chou, Fang-Yi / Cheng, Sin-Jhong / Chen, Hui-Mei / Jin, Lee-Way / Carvalho, Kevin / Huin, Vincent / Buée, Luc / Liao, Yung-Feng / Lin, Chun-Jung / Blum, David / Chern, Yijuang

Acta neuropathologica communications

2021 Volume 9, Issue 1, Page(s) 112

Abstract: Tau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer's disease (AD). Earlier reports showed that adenosine metabolism is abnormal in the brain of AD patients while consequences ... ...

Abstract	Tau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer's disease (AD). Earlier reports showed that adenosine metabolism is abnormal in the brain of AD patients while consequences remained ill-defined. Herein, we aimed at investigating whether manipulation of adenosine tone would impact Tau pathology, associated molecular alterations and subsequent neurodegeneration. We demonstrated that treatment with an inhibitor (J4) of equilibrative nucleoside transporter 1 (ENT1) exerted beneficial effects in a mouse model of Tauopathy. Treatment with J4 not only reduced Tau hyperphosphorylation but also rescued memory deficits, mitochondrial dysfunction, synaptic loss, and abnormal expression of immune-related gene signatures. These beneficial effects were particularly ascribed to the ability of J4 to suppress the overactivation of AMPK (an energy reduction sensor), suggesting that normalization of energy dysfunction mitigates neuronal dysfunctions in Tauopathy. Collectively, these data highlight that targeting adenosine metabolism is a novel strategy for tauopathies.
MeSH term(s)	Animals ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Disease Models, Animal ; Equilibrative Nucleoside Transporter 1/antagonists & inhibitors ; Humans ; Mice ; Tauopathies/metabolism ; Tauopathies/pathology
Chemical Substances	Equilibrative Nucleoside Transporter 1
Language	English
Publishing date	2021-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-021-01213-7
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Article: Quantitative measurement of γ-secretase-mediated amyloid precursor protein and notch cleavage in cell-based luciferase reporter assay platforms

Wang, Bo-Jeng / Wu, Pei-Yi / Chen, Yun-Wen / Chang, Yu-Tzu / Bhore, Noopur / Wu, Po-Fan / Liao, Yung-Feng

Journal of visualized experiments. 2018 Jan. 25, , no. 131

2018

Abstract	We have developed a pair of cell-based reporter gene assays to quantitatively measure γ-secretase cleavage of distinct substrates. This manuscript describes procedures that may be used to monitor γ-secretase-mediated cleavage of either APP-C99 or Notch, using a Gal4 promoter-driven firefly luciferase reporter system. These assays were established by stably co-transfecting HEK293 cells with the Gal4-driven luciferase reporter gene and either the Gal4/VP16-tagged C-terminal fragment of APP (APP-C99; CG cells), or the Gal4/VP16-tagged Notch-ΔE (NΔE; NG cells). Using these reporter assays in parallel, we have demonstrated that an ErbB2 inhibitor, CL-387,785, can preferentially suppress γ-secretase cleavage of APP-C99 in CG cells, but not NΔE in NG cells. The differential responses exhibited by the CG and NG cells, when treated with CL-387,785, represent a preferred characteristic for γ-secretase modulators, and these responses are in stark contrast to the pan-inhibition of γ-secretase induced by DAPT. Our studies provide direct evidence that γ-secretase activities toward different substrates can be differentiated in a cellular context. These new assays may therefore be useful tools in drug discovery for improved AD therapies.
Keywords	amyloid ; drugs ; enzyme activity ; luciferase ; quantitative analysis ; reporter genes
Language	English
Dates of publication	2018-0125
Size	p. e56795.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/56795
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