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a(HBP:HBP00006)

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Entity

Name
HBP00006
Namespace
HBP
Namespace Version
20181029
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/785431732a26d6809b4162d98b95687d16404e63/export/hbp.belns

Appears in Networks 5

Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5 v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease v0.1.0

A small assortment of academic articles describing quantitatively described interactions between the MAPT (Tau) protein and small molecules

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer’s disease brain v1.0.1

In-Edges 24

p(HGNC:CDK5) association a(HBP:HBP00006) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(FPLX:ERK) association a(HBP:HBP00006) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(FPLX:GSK3) association a(HBP:HBP00006) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:PRKACA) association a(HBP:HBP00006) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"alpha,alpha-trehalose") decreases a(HBP:HBP00006) View Subject | View Object

It also proved effective in cellu- lar models of PD, HD and AD 121,122 , as well as in mouse models of HD, AD and tauopathies, where it cleared aggregates, reduced neurodegeneration and ameliorated motor and cognitive performance 123–125 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

a(CHEBI:Temsirolimus) decreases a(HBP:HBP00006) View Subject | View Object

Likewise, temsirolimus reduced the accumulation of phosphorylated tau in SH-SY5Y cells and P301S tauopathy mice 137 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

a(HBP:HBP00020) decreases a(HBP:HBP00006) View Subject | View Object

Aminothienopyridazines (APTZs) Tau aggregation inhibitors (B/P: blood to plasma ratio). PubMed:23484434

Appears in Networks:

a(CHEBI:90) causesNoChange a(HBP:HBP00006) View Subject | View Object

Pyrogallol generic substitution pattern commonly found in multiple polyphenolic Tau aggregation inhibitors such as 12 and 19. Note the structural overlap with the inactive pyrocatechol-substituted epicatechin PubMed:23484434

Appears in Networks:

a(CHEBI:112284) decreases a(HBP:HBP00006) View Subject | View Object

Aminothienopyridazines (APTZs) Tau aggregation inhibitors (B/P: blood to plasma ratio). PubMed:23484434

Appears in Networks:

a(CHEBI:18152) decreases a(HBP:HBP00006) View Subject | View Object

Pyrogallol generic substitution pattern commonly found in multiple polyphenolic Tau aggregation inhibitors such as 12 and 19. Note the structural overlap with the inactive pyrocatechol-substituted epicatechin PubMed:23484434

Appears in Networks:

a(CHEBI:22580) decreases a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

a(CHEBI:3441) decreases a(HBP:HBP00006) View Subject | View Object

Representative examples of N-phenylamine Tau aggregation inhibitors and structural overlap with the Aβ40 aggregation inhibitor 33 or the nonsteroidal anti-inflammatory drug 34. PubMed:23484434

Appears in Networks:

a(CHEBI:3647) causesNoChange a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

a(CHEBI:44932) causesNoChange a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

a(CHEBI:4806) decreases a(HBP:HBP00006) View Subject | View Object

Pyrogallol generic substitution pattern commonly found in multiple polyphenolic Tau aggregation inhibitors such as 12 and 19. Note the structural overlap with the inactive pyrocatechol-substituted epicatechin PubMed:23484434

Appears in Networks:

a(CHEBI:6710) decreases a(HBP:HBP00006) View Subject | View Object

Representative examples of N-phenylamine Tau aggregation inhibitors and structural overlap with the Aβ40 aggregation inhibitor 33 or the nonsteroidal anti-inflammatory drug 34. PubMed:23484434

Appears in Networks:

a(CHEBI:6872) decreases a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

a(CHEBI:8028) causesNoChange a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

a(CHEBI:87637) decreases a(HBP:HBP00006) View Subject | View Object

Redox cycling of methylene blue and TAGI potencies. Upper panel (black): Reduced leuco form 2 and structural overlap with inactive phenothiazines 3, 4, and 5. Lower panel (blue): Structural overlap between oxidized form 1 and azure A (6), reduced anthraquinone, 8, and 9, showing the extended π-conjugated system (ND: not determined). PubMed:23484434

Appears in Networks:

p(MGI:Mapt, var("p.Pro301Leu")) increases a(HBP:HBP00006) View Subject | View Object

However, whereas the P301L mutation leads to tau aggregation into paired helical filaments (PHFs) (Barghorn et al., 2000), patients with the risk-associated A152T mutation display higher abundance of oligomers (Coppola et al., 2012) PubMed:29024336

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

p(HBP:HBP00053, var("p.Lys280del")) increases a(HBP:HBP00006) View Subject | View Object

Interestingly, a deletion of lysine 280 (hTau40 DK280), known to lead to tau aggregation (Khlistunova et al., 2006), turned this protein into a very poor CMA substrate (Fig. 6a,b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
Medium
MeSH
Brain

p(HBP:HBP00053, var("p.Lys280delinsProPro")) decreases a(HBP:HBP00006) View Subject | View Object

Thus, insertion of two prolines in the DK280 background (hTau40 DK280/2P), which prevents tau aggregation (Barghorn & Mandelkow, 2002), only partially rescued CMA uptake of the DK280 mutant (Fig. 6a,b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

p(HBP:HBP00056, var("p.Pro301Leu")) increases a(HBP:HBP00006) View Subject | View Object

SEC analysis of the molecular weight distribution of tau demonstrated that rTg21221 brain extracts (PBS-soluble, 3,000g) contained primarily LMW species and very low levels of HMW tau species, whereas rTg4510 brain extract showed both HMW and LMW peaks (Fig. 2e,f). PubMed:26458742

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases a(HBP:HBP00006) View Subject | View Object

The HMW tau species from the AD brain were highly phosphorylated compared with those from control brain (Fig. 6m). PubMed:26458742

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

Out-Edges 8

a(HBP:HBP00006) association p(HGNC:CDK5) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) association p(HGNC:PRKACA) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) association p(FPLX:ERK) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) association p(FPLX:GSK3) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) decreases act(complex(GO:"proteasome complex")) View Subject | View Object

Both aggregates and mutant forms of tau likewise block the proteasome, and its ability to degrade hyper- phosphorylated and oligomeric tau is reduced compared with its ability to degrade physiological tau 3,55,68 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HBP:HBP00006) decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HBP:HBP00006) increases tloc(p(HGNC:MAPT), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:Neurons)) View Subject | View Object

Importantly, neuronal uptake of HMW tau occurred in vivo as well; human tau uptake in neurons was detected in young rTg4510 (pre-tangle stage) (Fig. 1j–l) and WT (Supplementary Fig. 6) mice injected with the HMW SEC fraction of Tg4510 (12 months) brain extract, but not in those injected with the LMW fractions. PubMed:26458742

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) causesNoChange bp(GO:"cell death") View Subject | View Object

There was no difference in cell viability between tau-aggregate positive and negative cells for up to 4 days (Supplementary Fig. 10). PubMed:26458742

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.