The Prion pathways to brain disease
TSEs are characterised by neurodegeneration and eventually may lead to death. The PrP interactions form the pathway leading to such an outcome, but they remain poorly characterized. EU-funded project PRP and NEURODEGENER project sought to shed light on this pathway and identify what triggers neurodegeneration in mammalian brain cells. Researchers showed that PrP interact with the neural cell adhesion molecule (NCAM) and associate with NCAM at the neuronal cell surface. The interactions between NCAM and PrP promote neurite outgrowth. When these interactions are disrupted due to a pathogenic form of PrP or by PrP-antibodies, the NCAM/PrP-dependent neurite outgrowth is arrested. Lipid rafts are liquid-ordered membrane microdomains with a unique protein and lipid composition. They are found on the plasma membrane of most, if not all, mammalian cells and they function as signalling centres, due to a large number of signalling molecules that are concentrated there. They facilitate efficient and specific signal transduction. Experimental evidence has shown that NCAM co-localises with PrP these lipid rafts. The overall observations show that NCAM interacts with PrP suggesting that both proteins form a complex in lipid rafts. Such findings assist the efforts for the revelation of the mechanisms of neurodegeneration, providing the basis to new preventive and therapeutic strategies against TSEs.
