Alzheimer's Disease Pathway BioCarta

Preferred Label : Alzheimer's Disease Pathway BioCarta;

NCIt synonyms : BioCarta Alzheimers Disease Pathway;

NCIt related terms : Deregulation of CDK5 in Alzheimers Disease;

Alternative definition : BIOCARTA: Cyclin-dependent kinase 5 (cdk5), a multi-functional kinase, and its neuron-specific activator p35 are required for neurite outgrowth and cortical lamination. Proteolytic cleavage of p35 produces p25, which accumulates in the brains of patients with Alzheimer's disease. Conversion of p35 to p25 causes prolonged activation and mislocalization of cdk5 and the hyperphosphorylates tau, leading to the formation of paired helical filaments and promotion of apoptosis. In cultured primary cortical neurons, excitotoxins, hypoxic stress and calcium influx induce the production of p25. In fresh brain lysates, addition of calcium can stimulate cleavage of p35 to p25. Specific inhibitors of calpain1 effectively inhibit the calcium-induced cleavage of p35. In vitro, calpain1 directly cleaves p35 to release a fragment with relative molecular mass 25,000. Application of the amyloid beta-peptide A beta induces the conversion of p35 to p25 in primary cortical neurons. Inhibition of cdk5 or calpain activity reduces cell death in A beta-treated cortical neurons. These observations indicate that cleavage of p35 to p25 by calpain may be involved in the pathogenesis of Alzheimer's disease. GSK3B also phosphorylates tau but does not induce hyperphosphorylation in response to calpain activating stimuli. Additionally, down-regulation or inhibition of PP2A increases the hyper-phosphorylation of tau. (This definition may be outdated - see the DesignNote.);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 Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate.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_p35alzheimersPathway;

Details

Origin ID

C39177;

UMLS CUI

C1511120;

Automatic exact mappings (from CISMeF team)
- Alzheimer's disease [LOINC component]
- alzheimer disease [MeSH Descriptor]
See also inter- (CISMeF)
- Alzheimer disease [ORDO Disease]
Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Amyloid-Beta Precursor Protein [NCIt concept]
- Calpain-1 Catalytic Subunit [NCIt concept]
- Calpain-2 Catalytic Subunit [NCIt concept]
- Casein Kinase I Isoform Alpha [NCIt concept]
- Cyclin-Dependent Kinase 5 [NCIt concept]
- Cyclin-Dependent Kinase 5 Activator 1 [NCIt concept]
- Glycogen Synthase Kinase-3 Beta [NCIt concept]
- Serine/Threonine-Protein Phosphatase 2A Regulatory Subunit B'' Subunit Beta [NCIt concept]
pathway_has_gene_element
- APP wt Allele [NCIt concept]
- CAPN1 wt Allele [NCIt concept]
- CAPN2 wt Allele [NCIt concept]
- CDK5 wt Allele [NCIt concept]
- CDK5R1 wt Allele [NCIt concept]
- CSNK1A1 wt Allele [NCIt concept]
- GSK3B wt Allele [NCIt concept]
- PPP2R3B wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

Main resources

You can consult :

recommendations
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documents for patients