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PubMed: 27087442

Title
APOE4 Induces Site-Specific Tau Phosphorylation Through Calpain-CDK5 Signaling Pathway in EFAD-Tg Mice.
Journal
Current Alzheimer research
Volume
13
Issue
None
Pages
1048-55
Date
2016-01-01
Authors
Zhu Y | Zhou M | Chen X | Collins N | Dai X | Huang T | LaDu MJ | Lin L | Shen H | Wei Z | Wu X | Xiao N | York J | Zhang J

Evidence 7c0bde3e72
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We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8).

a(CHEBI:"glutamate(1-)") increases p(HBP:"CDK5R1 p25") View Subject | View Object

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Uberon
hippocampal formation

p(HBP:"CDK5R1 p25") positiveCorrelation p(HBP:"Tau epitope, AT8") View Subject | View Object

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Uberon
hippocampal formation

p(HBP:"Tau epitope, AT8") positiveCorrelation p(HBP:"CDK5R1 p25") View Subject | View Object

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Uberon
hippocampal formation

Evidence a4e53af880
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Our data showed that CDK5 knock down induced an increase in p35 protein levels and Rac activity in triple transgenic Alzheimer's mice, which correlated with the recovery of cognitive function; these findings confirm that increased p35 and active Rac are involved in neuroprotection. In summary, our data suggest that p35 acts as a mediator of Rho GTPase activity and contributes to the neuroprotection induced by CDK5 RNAi.

act(a(MESH:Neurons)) positiveCorrelation p(MGI:Cdk5r1) View Subject | View Object

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act(a(MESH:Neurons)) positiveCorrelation act(p(HBP:RAC1b)) View Subject | View Object

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act(a(MESH:Neurons)) negativeCorrelation p(MGI:Cdk5) View Subject | View Object

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act(p(HBP:RAC1b)) negativeCorrelation p(MGI:Cdk5) View Subject | View Object

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act(p(HBP:RAC1b)) positiveCorrelation act(a(MESH:Neurons)) View Subject | View Object

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p(MGI:Cdk5) negativeCorrelation p(MGI:Cdk5r1) View Subject | View Object

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p(MGI:Cdk5) negativeCorrelation act(p(HBP:RAC1b)) View Subject | View Object

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p(MGI:Cdk5) negativeCorrelation path(MESH:Cognition) View Subject | View Object

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p(MGI:Cdk5) negativeCorrelation act(a(MESH:Neurons)) View Subject | View Object

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p(MGI:Cdk5r1) negativeCorrelation p(MGI:Cdk5) View Subject | View Object

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p(MGI:Cdk5r1) positiveCorrelation act(a(MESH:Neurons)) View Subject | View Object

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path(MESH:Cognition) negativeCorrelation p(MGI:Cdk5) View Subject | View Object

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Evidence 666e2b48d8
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The levels of CDK5, its regulatory subunits (p35 and p25) and calpain (including calpain1 and calpain2), but not GSK3ß, were significantly increased in E4FAD mice compared to E3FAD mice.

p(HBP:"APOE e4") increases p(MGI:Capn2) View Subject | View Object

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p(HBP:"APOE e4") increases p(MGI:Cdk5) View Subject | View Object

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p(HBP:"APOE e4") increases p(HBP:"CDK5R1 p25") View Subject | View Object

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p(HBP:"APOE e4") increases p(MGI:Cdk5r1) View Subject | View Object

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p(HBP:"APOE e4") increases p(MGI:Capn1) View Subject | View Object

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p(HBP:"APOE e4") causesNoChange p(MGI:Gsk3b) View Subject | View Object

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