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PubMed: 30640040

Title
Screening of a neuronal cell model of tau pathology for therapeutic compounds.
Journal
Neurobiology of aging
Volume
76
Issue
None
Pages
24-34
Date
2019-04-01
Authors
Denner P | Fava E | Kitanovic A | Kurkowsky B | Mandelkow E | Möhl C | Pickhardt M | Tassoni M

Evidence 88b3036d50
JSON

As shown before, Tau aggregation (on the level of oligomeric and/or fibril aggregates) is toxic for cells.

a(HBP:"Tau aggregates") increases bp(GO:"cell killing") View Subject | View Object

Appears in Networks:

Evidence b4cb85983f
JSON

Tab. 1A-B: Summary of the Tau aggregation modulators (inhibitors = 18 (A), stimulators = 10 (B)) which show decrease / increase in the amount of ThS + cells without affecting the expression level of TauRD∆K compared to the compound untreated control.

a(PUBCHEM:10341154) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:10341154) association p(HGNC:MAPK14) View Subject | View Object

Appears in Networks:

a(PUBCHEM:10435235) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:10435235) decreases act(p(FPLX:"Gamma_secretase")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:11154925) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:11154925) association p(HGNC:KDR) View Subject | View Object

Appears in Networks:

a(PUBCHEM:11234052) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:11234052) association p(HGNC:KDR) View Subject | View Object

Appears in Networks:

a(PUBCHEM:11570805) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:11570805) association p(HGNC:MAPK14) View Subject | View Object

Appears in Networks:

a(PUBCHEM:11655119) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:11655119) association p(HGNC:TGFBR1) View Subject | View Object

Appears in Networks:

a(PUBCHEM:11655119) association p(HGNC:TGFBR2) View Subject | View Object

Appears in Networks:

a(PUBCHEM:156422) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:156422) association p(HGNC:MAPK14) View Subject | View Object

Appears in Networks:

a(PUBCHEM:24756910) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:24756910) association p(FPLX:"HDAC_I") View Subject | View Object

Appears in Networks:

a(PUBCHEM:24756910) association p(FPLX:"HDAC_II") View Subject | View Object

Appears in Networks:

a(PUBCHEM:24756910) association p(HGNC:EGFR) View Subject | View Object

Appears in Networks:

a(PUBCHEM:24756910) association p(HGNC:ERBB2) View Subject | View Object

Appears in Networks:

a(PUBCHEM:2746) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:2746) association p(FPLX:"HDAC_I") View Subject | View Object

Appears in Networks:

a(PUBCHEM:3033825) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:3033825) association p(HGNC:TNC) View Subject | View Object

Appears in Networks:

a(PUBCHEM:4261) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:4261) association p(HGNC:HDAC1) View Subject | View Object

Appears in Networks:

a(PUBCHEM:4261) association p(HGNC:HDAC3) View Subject | View Object

Appears in Networks:

a(PUBCHEM:42640) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:42640) association p(HGNC:MDM4) View Subject | View Object

Appears in Networks:

a(PUBCHEM:447966) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:447966) association p(HGNC:TGFBR1) View Subject | View Object

Appears in Networks:

a(PUBCHEM:448537) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:448537) association p(FPLX:ESR) View Subject | View Object

Appears in Networks:

a(PUBCHEM:4521392) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:4521392) association p(HGNC:TGFBR1) View Subject | View Object

Appears in Networks:

a(PUBCHEM:46209426) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:46209426) association p(FPLX:ROCK) View Subject | View Object

Appears in Networks:

a(PUBCHEM:4878) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:4878) association p(HGNC:LCK) View Subject | View Object

Appears in Networks:

a(PUBCHEM:4878) association p(HGNC:FYN) View Subject | View Object

Appears in Networks:

a(PUBCHEM:49806720) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:49806720) decreases act(p(HGNC:ALK)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:5311272) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:5311272) decreases act(p(FPLX:"Gamma_secretase")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:5318517) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:5318517) association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:

a(PUBCHEM:5318517) association p(FPLX:Actin) View Subject | View Object

Appears in Networks:

a(PUBCHEM:53340666) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:53340666) association p(HGNC:HDAC6) View Subject | View Object

Appears in Networks:

a(PUBCHEM:5833) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:5833) association p(HGNC:AR) View Subject | View Object

Appears in Networks:

a(PUBCHEM:6321424) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:6321424) increases act(p(HGNCGENEFAMILY:"Chloride channel accessory")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:71295844) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:71295844) association p(HGNC:GSK3A) View Subject | View Object

Appears in Networks:

a(PUBCHEM:71295844) association p(HGNC:GSK3B) View Subject | View Object

Appears in Networks:

a(PUBCHEM:71729974) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:71729974) association p(HGNCGENEFAMILY:"Lysine demethylases") View Subject | View Object

Appears in Networks:

a(PUBCHEM:9839311) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:9839311) association p(HGNC:SELE) View Subject | View Object

Appears in Networks:

a(PUBCHEM:9839311) association p(HGNC:ICAM1) View Subject | View Object

Appears in Networks:

a(PUBCHEM:9865515) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:9865515) association p(FPLX:HDAC) View Subject | View Object

Appears in Networks:

a(PUBCHEM:9880) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

a(PUBCHEM:9880) decreases act(p(HGNC:AR)) View Subject | View Object

Appears in Networks:

p(FPLX:"HDAC_I") association a(PUBCHEM:24756910) View Subject | View Object

Appears in Networks:

p(FPLX:"HDAC_I") association a(PUBCHEM:2746) View Subject | View Object

Appears in Networks:

p(FPLX:"HDAC_II") association a(PUBCHEM:24756910) View Subject | View Object

Appears in Networks:

p(FPLX:Actin) association a(PUBCHEM:5318517) View Subject | View Object

Appears in Networks:

p(FPLX:ESR) association a(PUBCHEM:448537) View Subject | View Object

Appears in Networks:

p(FPLX:HDAC) association a(PUBCHEM:9865515) View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB) association a(PUBCHEM:5318517) View Subject | View Object

Appears in Networks:

p(FPLX:ROCK) association a(PUBCHEM:46209426) View Subject | View Object

Appears in Networks:

p(HGNC:AR) association a(PUBCHEM:5833) View Subject | View Object

Appears in Networks:

p(HGNC:EGFR) association a(PUBCHEM:24756910) View Subject | View Object

Appears in Networks:

p(HGNC:ERBB2) association a(PUBCHEM:24756910) View Subject | View Object

Appears in Networks:

p(HGNC:FYN) association a(PUBCHEM:4878) View Subject | View Object

Appears in Networks:

p(HGNC:GSK3A) association a(PUBCHEM:71295844) View Subject | View Object

Appears in Networks:

p(HGNC:GSK3B) association a(PUBCHEM:71295844) View Subject | View Object

Appears in Networks:

p(HGNC:HDAC1) association a(PUBCHEM:4261) View Subject | View Object

Appears in Networks:

p(HGNC:HDAC3) association a(PUBCHEM:4261) View Subject | View Object

Appears in Networks:

p(HGNC:HDAC6) association a(PUBCHEM:53340666) View Subject | View Object

Appears in Networks:

p(HGNC:ICAM1) association a(PUBCHEM:9839311) View Subject | View Object

Appears in Networks:

p(HGNC:KDR) association a(PUBCHEM:11154925) View Subject | View Object

Appears in Networks:

p(HGNC:KDR) association a(PUBCHEM:11234052) View Subject | View Object

Appears in Networks:

p(HGNC:LCK) association a(PUBCHEM:4878) View Subject | View Object

Appears in Networks:

p(HGNC:MAPK14) association a(PUBCHEM:11570805) View Subject | View Object

Appears in Networks:

p(HGNC:MAPK14) association a(PUBCHEM:156422) View Subject | View Object

Appears in Networks:

p(HGNC:MAPK14) association a(PUBCHEM:10341154) View Subject | View Object

Appears in Networks:

p(HGNC:MDM4) association a(PUBCHEM:42640) View Subject | View Object

Appears in Networks:

p(HGNC:SELE) association a(PUBCHEM:9839311) View Subject | View Object

Appears in Networks:

p(HGNC:TGFBR1) association a(PUBCHEM:4521392) View Subject | View Object

Appears in Networks:

p(HGNC:TGFBR1) association a(PUBCHEM:447966) View Subject | View Object

Appears in Networks:

p(HGNC:TGFBR1) association a(PUBCHEM:11655119) View Subject | View Object

Appears in Networks:

p(HGNC:TGFBR2) association a(PUBCHEM:11655119) View Subject | View Object

Appears in Networks:

p(HGNC:TNC) association a(PUBCHEM:3033825) View Subject | View Object

Appears in Networks:

p(HGNCGENEFAMILY:"Lysine demethylases") association a(PUBCHEM:71729974) View Subject | View Object

Appears in Networks:

Evidence f011744b02
JSON

Treatment with Givinostat (1.2 µM) lead to a nearly 7-fold increase in the fraction of ThS + cells (from ~ 12% to ~ 84%, Fig. S4A and B, blue lines) compared to the uninduced control, and 2.5-fold compared to the induced control.

a(PUBCHEM:9804992) decreases act(p(FPLX:HDAC)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:9804992) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence d00eb97691
JSON

Conversely, compounds related to HDAC inhibition (16 of 20) led to enhanced Tau aggregation, suggesting that HDAC activity is important for suppressing aggregation

act(p(FPLX:HDAC)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence b8b0708f78
JSON

The dose response screening identified compounds related to the inhibition of 3 major targets led to inhibition of Tau aggregation: p38 MAPK (7 out of 8 compounds in the initial library), VEGFR1/2 (3 of 8) and TGF (3 of 10).

act(p(FPLX:TGFB)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

act(p(HGNC:FLT1)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

act(p(HGNC:KDR)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

act(p(HGNC:MAPK14)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.