Gene Set: BIOCARTA_P35ALZHEIMERS_PATHWAY

Standard name BIOCARTA_P35ALZHEIMERS_PATHWAY
Systematic name M12718
Brief description Deregulation of CDK5 in Alzheimers Disease
Full description or abstract 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 promotes 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 phosphoryklates 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.
Collection C2: curated gene sets
      CP: canonical pathways
            CP:BIOCARTA: BioCarta gene sets
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External links https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_p35AlzheimersPathwa...
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Organism Homo sapiens
Contributed by BioCarta
Source platform Human_RefSeq
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Version history 7.0: Changed members. Upgraded to final version of Biocarta.

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