General Information:

Id: 418
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
brain
article
Reference: Lee HK et al.(2009) The insulin/Akt signaling pathway is targeted by intracellular beta-amyloid. Mol. Biol. Cell 20: 1533-1544 [PMID: 19144826]

Interaction Information:

Comment Type II diabetes and peripheral insulin resistance are risk factors for Alzheimer disease.
Formal Description
Interaction-ID: 1830

increases_activity of

Comment Type II diabetes and peripheral insulin resistance are risk factors for Alzheimer disease.
Formal Description
Interaction-ID: 1834

phenotype

insulin resistance

increases_activity of

Comment Intraneuronal beta-amyloid accumulates early in Alzheimer disease and inclusion body myositis.
Formal Description
Interaction-ID: 1876

increases_quantity of

gene/protein

Amyloid beta peptide

Comment In Alzheimer brain the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control.
Formal Description
Interaction-ID: 1878

decreases_activity of

protein modification

AKT1-phos

Comment AKT1 interacts with PDPK1.
Formal Description
Interaction-ID: 1890

gene/protein

AKT1

interacts (colocalizes) with

gene/protein

PDPK1

Drugbank entries Show/Hide entries for AKT1 or PDPK1
Comment The Akt-1-binding partner HSP27 showed no changes in interaction level with disease state.
Formal Description
Interaction-ID: 1892

NOT affects_activity of

process

AKT1/HSPB1 binding

Comment AKT1 is localized in brain.
Formal Description
Interaction-ID: 1943

gene/protein

AKT1

is localized in

tissue/cell line

brain

Drugbank entries Show/Hide entries for AKT1
Comment In AD frontal lobe, p-Akt (Thr308) levels were decreased relative to control.
Formal Description
Interaction-ID: 1950

decreases_quantity of

protein modification

AKT1-phosThr308

in AD frontal lobe
Comment One possibility for the down-regulation of Akt activation in AD brain is direct inhibition mediated by an increase in cellular beta-amyloid.
Formal Description
Interaction-ID: 1954

gene/protein

Amyloid beta peptide

decreases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment The association of beta-amyloid with each of Akt1 and PDK was increased in AD brain. Beta-amyloid has specific affinity for PDK/Akt.
Formal Description
Interaction-ID: 1955

gene/protein

Amyloid beta peptide

interacts (colocalizes) with

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment Another kinase with activity to regulate GSK, PKA, was not affected in the AD samples, confirming specificity.
Formal Description
Interaction-ID: 1973

NOT affects_activity of

complex/PPI

Protein kinase A

Comment Ser473 phosphorylation is required for full Akt activity and precedes the phosphorylation of Thr308 by PDK-1.
Formal Description
Interaction-ID: 1976

gene/protein

PDPK1

increases_phosphorylation of

gene/protein

AKT1

at Thr308; phosphorylation at Ser473 is required for full Akt activity;
Drugbank entries Show/Hide entries for PDPK1 or AKT1
Comment Phosphorylation of tau and neurofilament proteins are elevated in AD.
Formal Description
Interaction-ID: 1983

increases_phosphorylation of

gene/protein

MAPT

Comment Phosphorylation of tau and neurofilament proteins are elevated in AD.
Formal Description
Interaction-ID: 1984

increases_phosphorylation of

gene/protein

neurofilament protein

Comment The association of beta-amyloid with each of Akt1 and PDK was increased in AD brain.
Formal Description
Interaction-ID: 14040

gene/protein

Amyloid beta peptide

interacts (colocalizes) with

gene/protein

PDPK1

Drugbank entries Show/Hide entries for PDPK1
Comment Intraneuronal beta-amyloid accumulates early in Alzheimer disease and inclusion body myositis.
Formal Description
Interaction-ID: 14041

phenotype

inclusion body myositis

increases_quantity of

gene/protein

Amyloid beta peptide

Comment In Alzheimer brain the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control.
Formal Description
Interaction-ID: 50452

decreases_quantity of

protein modification

AKT1-phos

in AD brain