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PubMed: 25887395

Title
Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation.
Journal
The Journal of biological chemistry
Volume
290
Issue
None
Pages
14893-903
Date
2015-06-12
Authors
Bieschke J | Diamond MI | Holmes BB | Mirbaha H | Sanders DW

Evidence 3ca4f53654
JSON

Heparin blocks Tau binding by masking HSPG binding sites on Tau, and sodium chlorate inhibits HSPG sulfation.

a(CHEBI:"sodium chlorate") decreases complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) View Subject | View Object

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a(CHEBI:heparin) decreases complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) View Subject | View Object

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Evidence 89b13a905e
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To test whether HSPGs also mediate BD Tau seeding, we titrated heparin and sodium chlorate, which inhibited seeding of all species (Fig. 8D).

a(CHEBI:"sodium chlorate") decreases a(HBP:"Tau aggregates") View Subject | View Object

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a(CHEBI:heparin) decreases a(HBP:"Tau aggregates") View Subject | View Object

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Evidence fe32196adc
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Whereas control brain homogenate exhibited mainly Tau monomer, the AD brain contained a range of Tau assemblies ranging from n = 1 to n > 20 (Fig. 7, A and B).

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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Annotations
MeSH
Brain

Evidence 6d3b361f2d
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Heparan sulfate proteoglycans (HSPGs) are cell surface pro- teins that bind Tau fibrils and are required for their uptake and seeding (10).

complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) increases tloc(a(HBP:"Tau fibrils"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

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complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) increases a(HBP:"Tau aggregates") View Subject | View Object

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Evidence c51d6f250b
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Within the limits of our detection, neither monomer nor dimer was internalized (Fig. 5, A and B). By contrast, trimers and larger species were readily internalized, with trimer uptake being slightly less efficient (Fig. 5, A and B). We did not observe an upper limit of size in terms of uptake.

complex(p(HGNC:MAPT), p(HGNC:MAPT), p(HGNC:MAPT)) increases tloc(a(HBP:"Tau fibrils"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

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Evidence b5760ee55e
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Only Tau RD oligomers of n  3 increased luciferase signal, defining these assemblies as the minimal size sufficient for spontaneous cell uptake and seeding (Fig. 6C).

complex(p(HGNC:MAPT), p(HGNC:MAPT), p(HGNC:MAPT)) increases a(HBP:"Tau aggregates") View Subject | View Object

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Evidence d1e83a3838
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Next we analyzed fractions for seeding activity in the P301S- Nluc/Cluc HEK293 cell lines by a split-luciferase complemen- tation assay, comparing AD and control brains. Trimers and larger BD Tau assemblies induced intracellular aggregation, but not monomer or dimer.

complex(p(HGNC:MAPT), p(HGNC:MAPT), p(HGNC:MAPT)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence f322b280a1
JSON

Tau RD fibrillizes very efficiently in vitro, making it ideal for fundamental studies (13).

p(HGNC:MAPT, frag("243_375")) increases a(HBP:"Tau fibrils") View Subject | View Object

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