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p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del"))

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Entity

Name
Tau isoform F (441 aa)
Namespace
HBP
Namespace Version
20181128
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/7e4be528f12abd28be768b62402fba6e083eaf9e/export/hbp-names.belns

Appears in Networks 2

Adenosine A1 receptor antagonist 64627 alleviates axonopathy caused by human Tau ΔK280 v1.0.0

Anti-aggregant tau mutant promotes neurogenesis v1.0.0

In-Edges 10

p(HBP:"Tau isoform F (441 aa)") hasVariant p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

Appears in Networks:

a(GO:"somatodendritic compartment") association p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

In organotypic hippocampal slices, both proaggregant and antiaggregant Tau is missorted to the somatodendritic compartment as has been shown before (Fig. 1 A and B, asterisks) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Hippocampus

a(HBP:"Tau epitope, 12E8") association p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

When corrected for the difference in total Tau, 12E8 phosphorylation does not differ between proaggregant and antiaggregant Tau (Fig. 2C) PubMed:27671637

Appears in Networks:

a(HBP:"Tau epitope, AT180") negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

The antibody AT180 (Tau pThr231) (18) shows (very) weak staining in the cell soma of both types of Tau transgenic slices (Fig. 2 G and H, asterisks) contrasting the high degree of Tau phosphorylated at Ser202/Thr205 [asterisks (somata) and long arrows (apical dendrites)] (AT8 antibody, Fig. 2 I and J) PubMed:27671637

Appears in Networks:

a(HBP:"Tau epitope, AT8") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

The antibody AT180 (Tau pThr231) (18) shows (very) weak staining in the cell soma of both types of Tau transgenic slices (Fig. 2 G and H, asterisks) contrasting the high degree of Tau phosphorylated at Ser202/Thr205 [asterisks (somata) and long arrows (apical dendrites)] (AT8 antibody, Fig. 2 I and J) PubMed:27671637

Appears in Networks:

a(HBP:"Tau epitope, PHF1") association p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

The PHF-1 epitope (pSer396+pSer404, Fig. 2 D–F) is seen in both types of Tau transgenic slices where it appears in the somatodendritic compartment (asterisks) and in the axonal grains (arrowheads) PubMed:27671637

Appears in Networks:

composite(a(PUBCHEM:64627), p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del"))) hasComponent p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

Appears in Networks:

a(CHEBI:doxycycline) decreases p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

However, when the expression of the antiaggregant TauRDΔKPP was switched off by DOX, there was an even more pronounced reduction in Wnt5a level (Fig. 10a, lane 3, bar 3) PubMed:29202785

Appears in Networks:

a(CHEBI:doxycycline) decreases p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

Remarkably, this caused a 40% reduction of the Wnt3 level compared to control slices (Fig. 10b, lane 3, bar 3) PubMed:29202785

Appears in Networks:

act(a(MESH:Microglia)) negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) View Subject | View Object

In controls and anti-aggregant TauRDΔKPP slices, the microglia were mainly in the ramified form, in contrast to the pro-aggregant TauRDΔK slices where microglia were more of the reactive form (Fig 3b) PubMed:29202785

Appears in Networks:

Out-Edges 35

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) association a(GO:"somatodendritic compartment") View Subject | View Object

In organotypic hippocampal slices, both proaggregant and antiaggregant Tau is missorted to the somatodendritic compartment as has been shown before (Fig. 1 A and B, asterisks) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases bp(GO:"protein localization to somatodendritic compartment") View Subject | View Object

In organotypic hippocampal slices, both proaggregant and antiaggregant Tau is missorted to the somatodendritic compartment as has been shown before (Fig. 1 A and B, asterisks) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) association a(HBP:"Tau epitope, 12E8") View Subject | View Object

When corrected for the difference in total Tau, 12E8 phosphorylation does not differ between proaggregant and antiaggregant Tau (Fig. 2C) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) association a(HBP:"Tau epitope, PHF1") View Subject | View Object

The PHF-1 epitope (pSer396+pSer404, Fig. 2 D–F) is seen in both types of Tau transgenic slices where it appears in the somatodendritic compartment (asterisks) and in the axonal grains (arrowheads) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) negativeCorrelation a(HBP:"Tau epitope, AT180") View Subject | View Object

The antibody AT180 (Tau pThr231) (18) shows (very) weak staining in the cell soma of both types of Tau transgenic slices (Fig. 2 G and H, asterisks) contrasting the high degree of Tau phosphorylated at Ser202/Thr205 [asterisks (somata) and long arrows (apical dendrites)] (AT8 antibody, Fig. 2 I and J) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) positiveCorrelation a(HBP:"Tau epitope, AT8") View Subject | View Object

The antibody AT180 (Tau pThr231) (18) shows (very) weak staining in the cell soma of both types of Tau transgenic slices (Fig. 2 G and H, asterisks) contrasting the high degree of Tau phosphorylated at Ser202/Thr205 [asterisks (somata) and long arrows (apical dendrites)] (AT8 antibody, Fig. 2 I and J) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange a(GO:"neurofibrillary tangle") View Subject | View Object

MC-1–positive Tau accumulates in the axonal grains of proaggregant Tau as described above (arrowheads), whereas antiaggregant slices remain unstained PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange a(GO:"dendritic spine") View Subject | View Object

Proaggregant Tau transgenic slices showed a significant reduction of spines compared with littermate control slices, whereas spine density of antiaggregant Tau transgenic slices was similar to controls (Fig. 3 A and B) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) decreases a(GO:mitochondrion) View Subject | View Object

Mitochondria transport is similar in both kinds of Tau transgenic slices (Fig. 3E) with only a moderately lower mitochondrial density in proaggregant Tau transgenic slices compared with antiaggregant slices (Fig. 3F and Table S2) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange act(a(GO:presynapse)) View Subject | View Object

We observed a typical paired-pulse facilitation (PPF) response in littermate controls and antiaggregant Tau transgenic slices, whereas in proaggregant Tau transgenic slices, the same stimulus paradigm resulted in a paired-pulse depression (Fig. 4B) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) decreases a(MESH:Axons) View Subject | View Object

The axonal density of mitochondria, which is slightly lower in proaggregant compared with antiaggregant Tau transgenic slices, is marginally decreased by 64627 treatment albeit in a genotype-independent manner (Fig. S7) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Mitochondria

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Hippocampus) View Subject | View Object

Microscopic analysis revealed a remarkable overall increase (30%) in the size of the hippocampus of anti-aggregant TauRDΔKPP OHSCs, compared to controls and the age-matched proaggregant TauRDΔK slices (Fig. 2a) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Hippocampus) View Subject | View Object

Additionally, there was an increase by 25% of the hippocampal volume in anti-aggregant TauRDΔKPP mice, compared to controls at P8 (Fig. 8c, bar 2), presumably due to the increased number of neurons PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Hippocampus) View Subject | View Object

The anti-aggregant TauRDΔKPP mice had an increased hippocampal volume of ~15% compared to agematched controls but it was not a significant increase as analyzed by bonferroni post hoc test (Fig. 9a, bar 2) in contrast mice expressing pro-aggregant TauRDΔK had a 25% reduced hippocampal volume (Fig. 9a, bar 3) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

This revealed an impressive increase in mature neurons in all regions of the hippocampus (47% in CA1; 69% in CA3 and 81% in DG) in the anti-aggregant TauRDΔKPP slices compared to age-matched controls (Fig. 2c, bars 2, 5 and 8) PubMed:29202785

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

Notably, after switch-off of antiaggregant TauRDΔKPP there was a change in the number of BrdU stained cells in all regions of the hippocampus (CA1 region 32%, CA3 region 22% and DG 33% reduction) compared to switch-ON conditions (Fig. 7a, bars 4, 8 and 12) PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA3 Region, Hippocampal
MeSH
Dentate Gyrus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

Similarly in the number of NeuN positive cells, there was a 22% reduction in CA1, 33% in CA3 and 37% reduction in DG compared to switch-On conditions (Fig. 7b, bars 4, 8 and 12) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

BrdU positive cells were present in CA1, CA3 and DG in both the controls and antiaggregant TauRDΔKPP groups (Fig. 8a, b), but their numbers were increased strongly by 80% only in the CA3 region of the anti-aggregant TauRDΔKPP mice (Fig. 8b, bar 4), with 20% change in the CA1 and no change in the DG (Fig. 8b, bar 2 and 6) PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA3 Region, Hippocampal
MeSH
Dentate Gyrus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

Additionally, there was an increase by 25% of the hippocampal volume in anti-aggregant TauRDΔKPP mice, compared to controls at P8 (Fig. 8c, bar 2), presumably due to the increased number of neurons PubMed:29202785

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

Surprisingly, the anti-aggregant TauRDΔKPP mice had an increased neuronal number significantly in the CA3 region (20%, Fig. 9b, bar 5), in contrast to the pro-aggregant TauRDΔK mice where neuronal loss (e.g. CA1 ~50%, CA3 ~10%, DG ~25%) was observed in all regions of the hippocampus (Fig. 9b, bar 3, 6, 9) PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:Neurons) View Subject | View Object

This suggests that the expression of anti-aggregant TauRDΔKPP is needed for the increased proliferation of newborn neurons, and since these new born neurons need endogenous mouse Tau for their migration, differentiation, and maturation, there is enhanced expression of endogenous mouse Tau PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases bp(GO:neurogenesis) View Subject | View Object

Thus, pro-aggregant TauRDΔK causes neurodegeneration, whereas anti-aggregant TauRDΔKPP leads to neurogenesis, even in regions outside the DG PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) negativeCorrelation act(a(MESH:Microglia)) View Subject | View Object

In controls and anti-aggregant TauRDΔKPP slices, the microglia were mainly in the ramified form, in contrast to the pro-aggregant TauRDΔK slices where microglia were more of the reactive form (Fig 3b) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) decreases a(MESH:Microglia) View Subject | View Object

Total numbers of Iba1 positive microglial cells were reduced to 50% in anti-aggregant TauRDΔKPP slices when compared to controls (Fig. 3c, bar 2) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange act(a(MESH:Microglia)) View Subject | View Object

The antiaggregant TauRDΔKPP slices had ramified form of microglia with 6-7 branches on an average indicating that the microglial cells were in their normal physiologically active form and there is no sign of inflammation (Fig 3d, bars 1 and 2). PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange path(MESH:Inflammation) View Subject | View Object

The antiaggregant TauRDΔKPP slices had ramified form of microglia with 6-7 branches on an average indicating that the microglial cells were in their normal physiologically active form and there is no sign of inflammation (Fig 3d, bars 1 and 2). PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases p(MGI:Mapt) View Subject | View Object

In the controls and the antiaggregant TauRDΔKPP slices there was a uniform axonal distribution of Tau in the hippocampus (Fig. 5, A1 and 2) PubMed:29202785

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases p(MGI:Mapt) View Subject | View Object

Surprisingly, there was an ~80% increase in the endogenous mouse Tau level in slices obtained from pups expressing anti-aggregant TauRDΔKPP (Fig. 5b lane 2 and 5c bar 2), compared with age matched non-transgenic controls and pro-aggregant TauRDΔK (Fig. 5b lane 1 and 3; and 5c lane 1 and 3) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases tloc(p(MGI:Mapt), fromLoc(GO:axon), toLoc(GO:"somatodendritic compartment")) View Subject | View Object

In spite of this increase, there was little mislocalization of Tau (endogenous or exogenous) into the somatodendritic compartment in the anti-aggregant TauRDΔKPP (Fig. 5, A2) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases p(MGI:Mapt) View Subject | View Object

From DIV15 until DIV30 the anti-aggregant slices were treated with DOX to switch off the expression of the anti-aggregant Tau. This lead to a strong reduction (~70%) of the endogenous mouse Tau (Fig. 10c, lane3) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases a(MESH:"Stem Cells") View Subject | View Object

However, in case of the anti-aggregant TauRDΔKPP slices there was a remarkable 30% increase in the number of BrdU positive cells in the CA1 and CA3 regions and almost 100% increase in DG (Fig. 6b, bar 2, 5, and 8) PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA3 Region, Hippocampal
MeSH
Dentate Gyrus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases bp(GO:"neuron differentiation") View Subject | View Object

In particular in the CA3 and DG regions almost 70% and in CA1 almost 50% of the new born cells got differentiated into NeuN positive neurons in the anti-aggregant TauRDΔKPP slices (Additional file 2: Figure S1A, bars 4, 8, 12).This reveals an increase in proliferation followed by an increase in neuronal differentiation in the anti-aggregant TauRDΔKPP slices PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA3 Region, Hippocampal
MeSH
Dentate Gyrus

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) decreases p(MGI:Wnt5a) View Subject | View Object

Surprisingly there was a 50% reduction in the amount of Wnt5a protein in anti-aggregant TauRDΔKPP slices compared to controls (Fig. 10a, lane 2, bar 2). PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases p(MGI:Wnt3) View Subject | View Object

Unexpectedly the Wnt3 levels in the anti-aggregant TauRDΔKPP slices were increased substantially (up to 85%) compared to the agematched control slices (Fig. 10b, lane 2, bar 2) PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) increases p(MGI:Wnt3) View Subject | View Object

Remarkably, this caused a 40% reduction of the Wnt3 level compared to control slices (Fig. 10b, lane 3, bar 3) PubMed:29202785

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.