Prion disease pathway (Homo sapiens)

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Prion diseases are rare, genetic, transmissible and sporadic diseases, which are caused by mutations in the PRNP gene. This gene is located on chromosome 20p13 and is composed of two exons. Mutations in the PRNP gene cause conformational changes in the prion protein (PRNP). The normal PRNP (protein) changes into the pathologic PRNP. A molecular pathway can give a better understanding in prion diseases.

This pathway is a prion disease pathway, that describes what happens when there is a mutation in the PRNP gene. The left part of the pathway represents the pathway retrieved from literature and the right part of the pathway represents data found using databases. The left part shos the interaction of pathological prion protein with an unknown receptor protein, this interaction activates a signalling pathway. The endoplasmic reticulum releases calcium and ER stress is induced. Activation of Caspase 12 by ER-stress is followed by cleavage and activation of the executioner Caspase-3, causing neuronal apoptosis. According to the databases, NCAM-1 can initiate two mechanisms: the activation of FGFR and formation of intracellular signalling complexes. NCAM-1 interacts with Fyn and FAK, resulting in phosphorylation of these two tyrosine kinases. Phosphorylation of Fyn and FAK results in activation of MAPK, ERK1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal