Role of cellular prion protein in interneuronal amyloid transmission.

Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a 'prion-like' spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases. The relevance of β-amyloid oligomers and cellular prion protein (PrP) binding has been a focus of interest in Alzheimer's disease (AD). At the molecular level, β-amyloid/PrP interaction takes place in two differently charged clusters of PrP. In addition to β-amyloid, participation of PrP in α-synuclein binding and brain spreading also appears to be relevant in α-synucleopathies. This review summarizes current knowledge about PrP as a putative receptor for amyloid proteins and the physiological consequences of these interactions.