General Information:

Id: 1,422
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
review
Reference: Rogers JT et al.(2008) Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimers disease Biochem. Soc. Trans. 36: 1282-1287 [PMID: 19021541]

Interaction Information:

Comment The essential metals iron, zinc and copper deposit near the Abeta (amyloid beta-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients.
Formal Description
Interaction-ID: 9877

drug/chemical compound

Iron

interacts (colocalizes) with

in the brain cortex of AD (Alzheimer's disease) patients
Comment APP was regulated at the translational level by active IL (interleukin)-1 (IL-1-responsive acute box) and IRE (iron-responsive element) RNA stem-loops in the 5' untranslated region of APP mRNA.
Formal Description
Interaction-ID: 9878

gene/protein

IL1B (active form)

affects_expression of

gene/protein

APP

at translational level
Drugbank entries Show/Hide entries for APP
Comment The essential metals iron, zinc and copper deposit near the Abeta (amyloid beta-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients.
Formal Description
Interaction-ID: 9880

drug/chemical compound

Zn2+

interacts (colocalizes) with

in the brain cortex of AD (Alzheimer's disease) patients
Comment The essential metals iron, zinc and copper deposit near the Abeta (amyloid beta-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients.
Formal Description
Interaction-ID: 9881

drug/chemical compound

Copper

interacts (colocalizes) with

in the brain cortex of AD (Alzheimer's disease) patients
Comment The APP IRE (iron-responsive element) is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability.
Formal Description
Interaction-ID: 9883

affects_activity of

gene/protein

ACO1

Comment Iron, in excess, is linked to neuron loss in the AD brain.
Formal Description
Interaction-ID: 9889

drug/chemical compound

Iron

affects_activity of

phenotype

neurodegeneration

Comment Haem binds Abeta (amyloid-beta-peptide) and has altered metabolism in the AD brain.
Formal Description
Interaction-ID: 9890

drug/chemical compound

Heme

interacts (colocalizes) with

gene/protein

Amyloid beta peptide

in AD brain
Drugbank entries Show/Hide entries for Heme
Comment Haem binds Abeta (amyloid-beta-peptide) and has altered metabolism in the AD brain.
Formal Description
Interaction-ID: 9892

affects_activity of

Comment Iron is localized in Haem.
Formal Description
Interaction-ID: 9893

drug/chemical compound

Iron

is localized in

drug/chemical compound

Heme

Drugbank entries Show/Hide entries for
Comment Iron and copper significantly enhanced the toxicity of Abeta in cultured neural cells.
Formal Description
Interaction-ID: 9894

drug/chemical compound

Iron

increases_activity of

phenotype

amyloidosis

in cultured neural cells
Comment Iron and copper significantly enhanced the toxicity of Abeta in cultured neural cells.
Formal Description
Interaction-ID: 9895

drug/chemical compound

Copper

increases_activity of

phenotype

amyloidosis

in cultured neural cells
Comment Elemental profiles (sulfur, iron, copper and zinc) were observed microscopically to physically associate with amyloid plaques.
Formal Description
Interaction-ID: 9897

drug/chemical compound

Sulfur

interacts (colocalizes) with

Comment Neurofibrillary tangles that are the second major hallmark of AD are negatively charged and capable of binding iron, which promotes further neurotoxicity during disease progression.
Formal Description
Interaction-ID: 9898

drug/chemical compound

Iron

interacts (colocalizes) with

Comment Brain metallothionein-III, a known potent copper/zinc-binding antioxidant protein, was measured to be lowered in the AD brain compared with control subjects.
Formal Description
Interaction-ID: 9951

decreases_quantity of

gene/protein

MT3

in brain
Comment Brain metallothionein-III, a known potent copper/zinc-binding antioxidant protein, was measured to be lowered in the AD brain compared with control subjects.
Formal Description
Interaction-ID: 9952

gene/protein

MT3

interacts (colocalizes) with

drug/chemical compound

Copper

Comment Brain metallothionein-III, a known potent copper/zinc-binding antioxidant protein, was measured to be lowered in the AD brain compared with control subjects.
Formal Description
Interaction-ID: 9954

gene/protein

MT3

interacts (colocalizes) with

drug/chemical compound

Zn2+

Comment Brain metallothionein-III, a known potent copper/zinc-binding antioxidant protein, was measured to be lowered in the AD brain compared with control subjects.
Formal Description
Interaction-ID: 9955

gene/protein

MT3

affects_activity of

Comment Secreted APP can act as an anti-coagulant by binding to Factor IXa, leading to the production of fibrinogen from fibrin.
Formal Description
Interaction-ID: 9960

gene/protein

APP

affects_activity of

process

coagulation

If APP is secreted
Drugbank entries Show/Hide entries for APP
Comment Secreted APP can act as an anti-coagulant by binding to factor IXa, leading to the production of fibrinogen from fibrin.
Formal Description
Interaction-ID: 9963

gene/protein

APP

interacts (colocalizes) with

gene/protein

Factor IXa

If APP is secreted
Drugbank entries Show/Hide entries for APP
Comment APP is increased after IL (interleukin)-1-mediated stress responses by translational up-regulation of APP mRNA translation at the same time by as induction of alpha-secretase activity to generate the 90 kDa APP(s) (alpha-secretase cleavage in the APP Abeta domain).
Formal Description
Interaction-ID: 9967

increases_expression of

gene/protein

APP

Drugbank entries Show/Hide entries for APP
Comment APP provides protection against catalysed oxidative stress.
Formal Description
Interaction-ID: 9976

gene/protein

APP

decreases_activity of

Drugbank entries Show/Hide entries for APP
Comment APP provides protection against catalysed oxidative stress.
Formal Description
Interaction-ID: 9979

gene/protein

APP

increases_activity of

process

neuroprotection

Drugbank entries Show/Hide entries for APP
Comment APP provides protection against catalysed oxidative stress.
Formal Description
Interaction-ID: 9982

process

neuroprotection

decreases_activity of

phenotype

neurodegeneration

Comment APP is increased after IL (interleukin)-1-mediated stress responses by translational up-regulation of APP mRNA translation at the same time by as induction of alpha-secretase activity to generate the 90 kDa APP(s) (alpha-secretase cleavage in the APP Abeta domain).
Formal Description
Interaction-ID: 9987

increases_activity of

gene/protein

Alpha-secretase

Comment Primary inflammatory cytokine induces the non-amyloidogenic secretion of APP(s) from astrocytes.
Formal Description
Interaction-ID: 10034

gene/protein

Cytokine

increases_activity of

Comment Primary inflammatory cytokine induces the non-amyloidogenic secretion of APP(s) from astrocytes.
Formal Description
Interaction-ID: 10036

increases_quantity of

gene/protein

APP

Drugbank entries Show/Hide entries for APP
Comment Primary inflammatory cytokine induces the non-amyloidogenic secretion of APP(s) from astrocytes.
Formal Description
Interaction-ID: 10037

increases_activity of

gene/protein

Cytokine

Comment The APP IRE (iron-responsive element) is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability.
Formal Description
Interaction-ID: 10049

affects_activity of

intracellular iron homeostasis is affected
Comment The APP IRE (iron-responsive element) is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability.
Formal Description
Interaction-ID: 10050

affects_activity of

gene/protein

IREB2