Alzheimer’s disease yield is associated with an abnormal build-up of amyloid-β (Aβ) peptides( 40-42 amino acids length) in the brain. Small, soluble aggregates of A β-A β oligomers – impair memory by disrupting memory-related functions of synaptic junctions between neurons. Lauren et al in Nature show that the prion protein might mediate the pathogenic effects of A-β oligomers.
The prion protein (PrP) is anchored to the cell membrane and associates with membrane microdomains called lipid rafts. It occurs in at least two conformational states. The cellular form, PrPc, is involved in maintaining the brain’s white matter, and in regulating this tissue’s innate immune cells, responses to oxidative stress and neuron formation. The highly pathogenic form, PrPsc, is a misfolded version of PrPc, and is resistant to enzymatic degradation. PrPsc is the main cause of a group of fatal neurodegenerative disorders called transmissible spongiforrn encephalopathies that includes Creutzfeldt-Iakob disease and mad cow disease.
A β binds to and influences the function of many cellular proteins. Lauren et al in their study conclude or suggest that Prpc itself acts as a receptor to to mediate the deleterious effects of the Aβ-42 oligomer.
Lauren et al 2009 Cellular prion mediates impairment of synaptic plasticity by amyloid- β oligomers Nature vol 457, pp 1128-1132
Cisse and Mucke 2009 A prion protein connection. Nature vol 457, pp 1090-1
Prions that cause brain disease may infect and move across the brain cells by travelling in the nano tubules and also dendrtic cells which connect these cells.
Nature 2009 prion highjackers vol 457 p 1060
- Martin Eastwood