Experimental models of prion-like protein propagation.

Abstract

Prion-like propagation has been proposed to underlie the pathogenesis and progression of many progressive neurodegenerative diseases, and considerable experimental evidence has been accumulated to support this idea. However, only limited evidence is available from the brains of patients, and it is not clear how well various experimental models reflect the clinical situation. In this review, I discuss experimental models of prion-like propagation, focusing on three major disease-associated intracellular proteins, α-synuclein, tau and transactivation response DNA-binding protein 43 kDa, which provide a molecular basis for evaluating the spread of pathologies in diseased brains, known as Braak staging. Although some issues remain, and further biochemical and structural analyses are needed, it seems clear that the concept of prion-like propagation is the key to understanding disease progression, as well as for the development of disease-modifying therapies.