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p(HBP:"Tau isoform F (441 aa)", 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 3

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

Anti-aggregant tau mutant promotes neurogenesis v1.0.0

Extracellular low-n oligomers of tau cause selective synaptotoxicity without affecting cell viability v1.0.0

In-Edges 21

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

Appears in Networks:

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

Appears in Networks:

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

We also observed that Tau missorts into a subgroup of proximal dendrites, which correlates with a dramatic spine loss in the affected dendrites (Fig. S2 C and F) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Dendrites

a(GO:"neurofibrillary tangle") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) 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:

a(GO:"somatodendritic compartment") association p(HBP:"Tau isoform F (441 aa)", 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.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.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.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.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:

a(HP:"Argyrophilic inclusion bodies") association p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Only proaggregant Tau transgenic slices reveal Taupositive beaded structures in the neuropil oriented mostly perpendicular to the apical dendrites of the CA1 pyramidal cells (Fig. 1 C and D, arrowheads) resembling grains in human AGD (16) PubMed:27671637

Appears in Networks:
Annotations
Cell Ontology (CL)
pyramidal neuron
MeSH
CA1 Region, Hippocampal

a(HP:"Argyrophilic inclusion bodies") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

This suggests that proaggregant Tau accumulates in the axons as grains PubMed:27671637

Appears in Networks:
Annotations
MeSH
Axons

a(MESH:"Presynaptic Terminals") causesNoChange p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

The axons of transfected neurons (Fig. 1 G and I) clearly reveal small inclusions of Tau (∼1 μm in size, arrowheads), although presynaptic boutons (e.g., giant mossy fiber boutons) are only marginally stained for Tau (Fig. 1I and Fig. S2 A and B; arrow), indicating that Tau does not accumulate at presynaptic boutons in these slices PubMed:27671637

Appears in Networks:

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

The axons of transfected neurons (Fig. 1 G and I) clearly reveal small inclusions of Tau (∼1 μm in size, arrowheads), although presynaptic boutons (e.g., giant mossy fiber boutons) are only marginally stained for Tau (Fig. 1I and Fig. S2 A and B; arrow), indicating that Tau does not accumulate at presynaptic boutons in these slices PubMed:27671637

Appears in Networks:

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

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

bp(GO:"astrocyte activation") negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

bp(GO:"response to oxidative stress") negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(MGI:Fos) negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(MGI:Gfap) negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(MGI:Hmox1) negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

act(a(MESH:Microglia)) positiveCorrelation p(HBP:"Tau isoform F (441 aa)", 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:

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

On the contrary, microglia in proaggregant TauRDΔK slices, were increased in number and were also observed with 2-3 branches on an average compared to age-matched controls and also the antiaggregant TauRDΔKPP slices (Fig. 3d, bar 3). This indicates that in the pro-aggregant TauRDΔK slices the microglia are in a reactive form, indicating that there is also enhanced inflammation PubMed:29202785

Appears in Networks:

Out-Edges 51

p(HBP:"Tau isoform F (441 aa)", 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.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.Lys280del")) association a(HP:"Argyrophilic inclusion bodies") View Subject | View Object

Only proaggregant Tau transgenic slices reveal Taupositive beaded structures in the neuropil oriented mostly perpendicular to the apical dendrites of the CA1 pyramidal cells (Fig. 1 C and D, arrowheads) resembling grains in human AGD (16) PubMed:27671637

Appears in Networks:
Annotations
Cell Ontology (CL)
pyramidal neuron
MeSH
CA1 Region, Hippocampal

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) positiveCorrelation a(HP:"Argyrophilic inclusion bodies") View Subject | View Object

This suggests that proaggregant Tau accumulates in the axons as grains PubMed:27671637

Appears in Networks:
Annotations
MeSH
Axons

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

The axons of transfected neurons (Fig. 1 G and I) clearly reveal small inclusions of Tau (∼1 μm in size, arrowheads), although presynaptic boutons (e.g., giant mossy fiber boutons) are only marginally stained for Tau (Fig. 1I and Fig. S2 A and B; arrow), indicating that Tau does not accumulate at presynaptic boutons in these slices PubMed:27671637

Appears in Networks:

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

We also observed that Tau missorts into a subgroup of proximal dendrites, which correlates with a dramatic spine loss in the affected dendrites (Fig. S2 C and F) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Dendrites

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

By contrast, dendrites that do not contain Tau are richly decorated with spines (>1 spines per μm), indicating that there is only local impairment of dendritic function in case of proaggregant Tau missorting PubMed:27671637

Appears in Networks:
Annotations
MeSH
Dendrites

p(HBP:"Tau isoform F (441 aa)", 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.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.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.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.Lys280del")) positiveCorrelation 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.Lys280del")) decreases bp(GO:"mitochondrial transport") View Subject | View Object

We determined mitochondrial movements in live organotypic slices because aggregation-prone Tau is known to impair mitochondrial transport (Fig. 3 D and E) PubMed:27671637

Appears in Networks:

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

ATP is reduced in the proaggregant transgenic slices, matching the lower mitochondrial density, compared with littermate controls or antiaggregant Tau transgenic slices (Fig. 3H) PubMed:27671637

Appears in Networks:

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

This suggests that the energy status of the neurons is compromised by proaggregant but not by antiaggregant Tau PubMed:27671637

Appears in Networks:
Annotations
MeSH
Neurons

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

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) negativeCorrelation p(MGI:Fos) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) negativeCorrelation bp(GO:"astrocyte activation") View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) negativeCorrelation p(MGI:Gfap) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) negativeCorrelation bp(GO:"response to oxidative stress") View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) negativeCorrelation p(MGI:Hmox1) View Subject | View Object

Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) decreases 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.Lys280del")) decreases bp(GO:"spontaneous synaptic transmission") View Subject | View Object

The slope of the input/output (I/O) curve is significantly reduced in proaggregant Tau transgenic mice compared with controls, indicative of impaired basal synaptic transmission (Fig. 5I) PubMed:27671637

Appears in Networks:
Annotations
MeSH
Mitochondria

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

This may be due to the strong Tau pathology of the toxic pro-aggregant TauRDΔK leading to Tau aggregation, loss of synapses and loss of neurons PubMed:29202785

Appears in Networks:

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

This may be due to the strong Tau pathology of the toxic pro-aggregant TauRDΔK leading to Tau aggregation, loss of synapses and loss of neurons PubMed:29202785

Appears in Networks:

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

This may be due to the strong Tau pathology of the toxic pro-aggregant TauRDΔK leading to Tau aggregation, loss of synapses and loss of neurons PubMed:29202785

Appears in Networks:

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

By contrast, the pro-aggregant TauRDΔK slices showed a pronounced reduction in neuronal numbers, particularly in the CA1 (-44%), CA3 (-33%) and DG (-22%) regions compared to controls (Fig. 2c, bars 3, 6 and 9) 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.Lys280del")) decreases 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
Hippocampus

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) increases path(HBP:Neurodegeneration) 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.Lys280del")) positiveCorrelation 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.Lys280del")) increases a(MESH:Microglia) View Subject | View Object

The opposite result was observed in the pro-aggregant TauRDΔK slices where the microglial number was increased by 100% compared to controls (Fig. 3c, bar 3) PubMed:29202785

Appears in Networks:

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

On the contrary, microglia in proaggregant TauRDΔK slices, were increased in number and were also observed with 2-3 branches on an average compared to age-matched controls and also the antiaggregant TauRDΔKPP slices (Fig. 3d, bar 3). This indicates that in the pro-aggregant TauRDΔK slices the microglia are in a reactive form, indicating that there is also enhanced inflammation PubMed:29202785

Appears in Networks:

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

On the contrary, microglia in proaggregant TauRDΔK slices, were increased in number and were also observed with 2-3 branches on an average compared to age-matched controls and also the antiaggregant TauRDΔKPP slices (Fig. 3d, bar 3). This indicates that in the pro-aggregant TauRDΔK slices the microglia are in a reactive form, indicating that there is also enhanced inflammation PubMed:29202785

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) increases path(MESH:Hypertrophy) View Subject | View Object

On the contrary the proaggregant TauRDΔK slices showed hypertrophic astrocytes with prominent cell bodies with 1-3 processes ranging from 3-5μm in length, which can be compared to the degrading forms of astrocytes (Fig. 4a3) PubMed:29202785

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

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

The pro-aggregant TauRDΔK slices showed intense mislocalization of Tau in the somato-dendritic compartment, the most affected being the CA3 pyramidal neurons (Fig. 5, A3) PubMed:29202785

Appears in Networks:

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

By contrast, pro-aggregant TauRDΔK slices showed no overall increase in endogenous mouse Tau (rather a 20% decrease), yet pronounced mislocalization (Fig. 5, A3). PubMed:29202785

Appears in Networks:

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

By contrast, pro-aggregant TauRDΔK slices showed no overall increase in endogenous mouse Tau (rather a 20% decrease), yet pronounced mislocalization (Fig. 5, A3). PubMed:29202785

Appears in Networks:

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

This was in striking contrast to the pro-aggregant TauRDΔK slices where there was no significant difference in the number of BrdU positive cells compared to the age matched controls (Fig. 6b, bar 3, 6, and 9) 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.Lys280del")) increases bp(GO:"neuron differentiation") View Subject | View Object

This also resulted in a 30% increase in the rate of differentiation in the CA1 region of the pro-aggregant TauRDΔK slices (Additional file 2: Fig. S1B, bars 2 and 4) PubMed:29202785

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) decreases 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.Lys280del")) decreases bp(GO:memory) View Subject | View Object

TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849

Appears in Networks:

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

TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849

Appears in Networks:

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

TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849

Appears in Networks:

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

Analysis of sarkosyl extracts of brain homogenates of mice expressing the pro-aggregant repeat domain TauRDΔK revealed that oligomers are present, partly in a disulfide–cross-linked form (Supplementary Fig. 1). PubMed:28528849

Appears in Networks:

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

During early stages of assembly, there is some increase in ThS intensity, combined with a pronounced increase in ANSfluorescence (Fig. 2Aand B), which is due to oligomers, indicating a change in conformation without increase in beta-structure PubMed:28528849

Appears in Networks:

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

As shown earlier, TauRDΔK-expressing mice display loss of neurons in the CA3 and other regions of the hippocampus [11,24]. PubMed:28528849

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) causesNoChange a(CHEBI:"reactive oxygen species") View Subject | View Object

By contrast, monomers of TauRDΔK even at 10 mM concentration did not cause any significant ROS increase (Fig. 5B). PubMed:28528849

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p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) causesNoChange bp(GO:"cellular calcium ion homeostasis") View Subject | View Object

By contrast, there was no significant increase in the calcium level in cells treated with TauRDΔK monomers even at higher concentration (10 mM) (Fig. 5E and F, green curves). PubMed:28528849

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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.