Is PrP the road to ruin?

EMBO J 30 10, 2057–2070 (2011); published online March 25 2011 Neurodegenerative disorders are one among the most debilitating diseases of an ageing population. Understanding the mechanisms of neuronal cell death during pathogenesis of diseases such as Alzheimer's, Parkinson's, Huntington's, and prion diseases is key to addressing the options for treatment and prevention of brain deterioration. One feature of many such diseases is the accumulation of specific misfolded proteins. Often these misfolded proteins take the form of large amyloid fibrils or plaques, but recent observations implicate small soluble oligomers as the primary causes of neuronal dysfunction. How these misfolded proteins trigger cell death pathways is largely unknown, but some reports have suggested mediation by normal cellular prion protein (PrP). In this issue, Resenberger et al (2011) provide evidence for membrane-anchored PrP's role in recognizing a variety of β-sheet-rich protein conformers and transducing pro-apoptotic signals.