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PubMed: 26118667

Title
Activation of Cdk5/p25 and tau phosphorylation following chronic brain hypoperfusion in rats involves microRNA-195 down-regulation.
Journal
Journal of neurochemistry
Volume
134
Issue
None
Pages
1139-51
Date
2015-09-01
Authors
Wang X | Sun LH | Ai J | Ban T | Bao YN | Chen QX | Hu XL | Jiang XM | Liu CD | Pei SC | Su XL | Sun LL | Yan ML | Zhao LJ | Zong DK

Evidence adb161fc20
JSON

Chronic Brain hypoperfusion (CBH) elevates nuclear factor-kB (NF-kB), which binds with the promoter sequences of miR-195 and negatively regulates its expression. Down-regulated miR-195 up-regulates APP and BACE1 and increases Aß levels. Some Aß then enter the intracellular space and activate calpain, promoting the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IkB (inhibitor of NF-?B)and directly phosphorylates Tau. Down-regulated miR-195 up-regulates p35, which provides the active substrates of p25

a(CHEBI:"amyloid-beta") negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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a(CHEBI:"amyloid-beta") increases p(INTERPRO:"Peptidase C2, calpain, catalytic domain") View Subject | View Object

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a(HBP:"Chronic cerebral hypoperfusion") increases p(FPLX:NFkappaB) View Subject | View Object

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complex(g(MIRBASE:"rno-mir-195"), p(FPLX:NFkappaB)) decreases m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(FPLX:NFkappaB) increases complex(g(MIRBASE:"rno-mir-195"), p(FPLX:NFkappaB)) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(RGD:App) View Subject | View Object

Appears in Networks:

m(MIRBASE:"rno-mir-195") negativeCorrelation p(RGD:Bace1) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(RGD:Cdk5r1) View Subject | View Object

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p(INTERPRO:"Peptidase C2, calpain, catalytic domain") positiveCorrelation act(p(RGD:Cdk5r1)) View Subject | View Object

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p(RGD:App) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(RGD:Bace1) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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act(p(RGD:Cdk5r1)) positiveCorrelation p(INTERPRO:"Peptidase C2, calpain, catalytic domain") View Subject | View Object

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p(RGD:Cdk5r1) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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Evidence 3d9f8700d5
JSON

The accumulation of p25 involves neurofibrillary tangle (NFT) formation via regulation of tau phosphorylation (Wen et al. 2007; Su and Tsai 2011)

a(GO:"neurofibrillary tangle") positiveCorrelation p(HBP:"CDK5R1 p25") View Subject | View Object

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p(HBP:"CDK5R1 p25") positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

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Evidence 68d46ebbc2
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We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi.

a(HBP:"Chronic cerebral hypoperfusion") increases p(RGD:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

a(HBP:"Chronic cerebral hypoperfusion") increases p(RGD:Mapt, pmod(Ph, Thr, 205)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

a(HBP:"Chronic cerebral hypoperfusion") increases p(RGD:Mapt, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

a(HBP:"Chronic cerebral hypoperfusion") increases p(RGD:Mapt, pmod(Ph, Thr, 231)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

a(HBP:"Chronic cerebral hypoperfusion") increases p(RGD:Mapt, pmod(Ph, Ser, 422)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

a(HBP:"Chronic cerebral hypoperfusion") increases p(HBP:"CDK5R1 p25") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

Evidence df95f94c63
JSON

A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3'UTR and inhibited p35 expression.

complex(g(RGD:Cdk5r1), m(MIRBASE:"rno-mir-195")) decreases r(RGD:Cdk5r1) View Subject | View Object

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m(MIRBASE:"rno-mir-195") increases complex(g(RGD:Cdk5r1), m(MIRBASE:"rno-mir-195")) View Subject | View Object

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Evidence c73dd329e6
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Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation.

m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

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m(MIRBASE:"rno-mir-195") negativeCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 422)) View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Ser, 202)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Ser, 262)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Ser, 422)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Thr, 205)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Thr, 231)) negativeCorrelation m(MIRBASE:"rno-mir-195") View Subject | View Object

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Evidence 7d4aacaed3
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To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain

complex(p(HGNC:CDK5), p(HGNC:CDK5R1)) increases act(p(HGNC:CDK5)) View Subject | View Object

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p(HGNC:CDK5) increases complex(p(HGNC:CDK5), p(HGNC:CDK5R1)) View Subject | View Object

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p(HGNC:CDK5R1) negativeCorrelation p(HBP:"CDK5R1 p25") View Subject | View Object

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p(HBP:"CDK5R1 p25") negativeCorrelation p(HGNC:CDK5R1) View Subject | View Object

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p(HBP:"CDK5R1 p25") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation p(HBP:"CDK5R1 p25") View Subject | View Object

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