General Information:

Id: 381
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
BTO:0000007 HEK-293 cell
article
Reference: Edbauer D et al.(2002) Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation. Proc. Natl. Acad. Sci. U.S.A. 99: 8666-8671 [PMID: 12048259]

Interaction Information:

Comment Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases: beta-secretase and gamma-secretase. Beta-secretase cuts at the N-terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut.
Formal Description
Interaction-ID: 1552

gene/protein

BACE1

increases_processing of

gene/protein

APP

Drugbank entries Show/Hide entries for BACE1 or APP
Comment Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases: beta-secretase and gamma-secretase. Beta-secretase cuts at the N-terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut.
Formal Description
Interaction-ID: 1564

complex/PPI

Gamma-secretase complex

increases_processing of

gene/protein

APP

Drugbank entries Show/Hide entries for APP
Comment Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Formal Description
Interaction-ID: 1588

gene/protein

PSEN1

affects_activity of

gene/protein

NCSTN

Comment Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Formal Description
Interaction-ID: 1589

gene/protein

NCSTN

affects_activity of

gene/protein

PSEN1

Comment Down-regulation of nicastrin by RNAi levels leads to a massive accumulation of the C-terminal fragments of the beta-amyloid precursor protein (APP); in addition, amyloid-beta production was markedly reduced (Abeta40 and Abeta42) by about 60%.
Formal Description
Interaction-ID: 1609

gene/protein

NCSTN

affects_quantity of

gene/protein

Amyloid beta peptide (40)

Comment PS1 preferentially binds mature Nct.
Formal Description
Interaction-ID: 1610

gene/protein

PSEN1

interacts (colocalizes) with

gene/protein

NCSTN

Comment Nicastrin (Nct) may provide an essential scaffold for the assembly and transport of the presenilin (PS) complex. If Nct is missing PS is destabilized, less PS complex is formed and consequently gamma-secretase activity is reduced.
Formal Description
Interaction-ID: 1617

gene/protein

NCSTN

increases_activity of

complex/PPI

Gamma-secretase complex

Comment Nicastrin (Nct) may provide an essential scaffold for the assembly and transport of the presenilin (PS) complex. If Nct is missing PS is destabilized, less PS complex is formed and consequently gamma-secretase activity is reduced.
Formal Description
Interaction-ID: 12968

gene/protein

NCSTN

affects_quantity of

complex/PPI

Gamma-secretase complex

Comment Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Formal Description
Interaction-ID: 14072

gene/protein

PSEN1

affects_quantity of

gene/protein

Amyloid beta peptide

Comment Down-regulation of nicastrin by RNAi levels leads to a massive accumulation of the C-terminal fragments of the beta-amyloid precursor protein (APP); in addition, amyloid-beta production was markedly reduced (Abeta40 and Abeta42) by about 60%.
Formal Description
Interaction-ID: 14074

gene/protein

NCSTN

affects_quantity of

gene/protein

Amyloid beta peptide (42)

Comment Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Formal Description
Interaction-ID: 14075

gene/protein

NCSTN

is_part_of

complex/PPI

Gamma-secretase complex

Comment Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Formal Description
Interaction-ID: 14076

gene/protein

PSEN1

is_part_of

complex/PPI

Gamma-secretase complex

Comment Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases: beta-secretase and gamma-secretase. Beta-secretase cuts at the N-terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut.
Formal Description
Interaction-ID: 21379

gene/protein

BACE1

affects_activity of

process

amyloid-beta formation

Drugbank entries Show/Hide entries for BACE1
Comment Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases: beta-secretase and gamma-secretase. Beta-secretase cuts at the N-terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut.
Formal Description
Interaction-ID: 21382

complex/PPI

Gamma-secretase complex

affects_activity of

process

amyloid-beta formation

Comment Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases: beta-secretase and gamma-secretase. Beta-secretase cuts at the N-terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut.
Formal Description
Interaction-ID: 21383

process

amyloid-beta formation

affects_quantity of

gene/protein

Amyloid beta peptide

Comment beta-Secretase and gamma-secretase affect the quantity of the different amyloid beta peptide types (Abeta40 and Abeta42) via processing of APP.
Formal Description
Interaction-ID: 21384

process

amyloid-beta formation

affects_quantity of

gene/protein

Amyloid beta peptide (40)

Comment beta-Secretase and gamma-secretase affect the quantity of the different amyloid beta peptide types (Abeta40 and Abeta42) via processing of APP.
Formal Description
Interaction-ID: 21385

process

amyloid-beta formation

affects_quantity of

gene/protein

Amyloid beta peptide (42)