Preferred Label : Amyloid Beta-Peptide Pathway;
NCIt related terms : Generation of amyloid b-peptide by PS1;
Alternative definition : BIOCARTA: Alzheimer's disease is associated with dense aggregations of proteins in
the brain called amyloid plaques that contain beta-amyloid fragments as a primary
component. If the development of amyloid plaques is responsible for neurodegeneration
in Alzheimer's disease, reduction of beta-amyloid formation may prevent the development
and progression of disease symptoms. Beta-amyloid fragments are derived from proteolytic
processing of amyloid precursor protein (APP) in neurons, and the subsequent release
of fragments into the extracellular space. APP in the ER is cleaved at residue 17
by alpha-secretase protease activity encoded by ADAM-10 and TACE. Beta-secretase activity,
recently identified as BACE, cleaves in the N-terminus of the beta-amyloid fragment.
Gamma-secretase cuts APP within the transmembrane domain at amino acids 40 and 42,
releasing the beta-amyloid fragment containing residues 1-40/42 as well as shorter
products such as p3 (residues 17-40/42) that requires alpha-secretase cleavage. The
gamma-secretase activity requires the transmembrane protein Presenilin-1 that is itself
cleaved into an N-terminal and C-terminal fragment that both are required for gamma-secretase
activity. Mutations in presenilin-1 have been genetically associated with familial
forms of Alzheimer's disease, further supporting the role of APP processing the development
of the disease. Inhibition of the beta- or gamma-secretases may provide a mechanism
to treat this disease. Other mechanisms may include altering degradation of beta-amyloid,
and the use of vaccines against beta-amyloid to remove aggregates. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_appPathway;
Origin ID : C38988;
UMLS CUI : C1510880;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
