PAR-1 for the Course of Neurodegeneration

The large number of kinases that phosphorylate the microtubule binding protein tau has posed a challenge to understanding their individual roles in turning this protein into a killer of neurons. A study in this issue of Cell(Nishimura et al., 2004...) uses an elegant fusion of loss-of-function genetics and transgenic overexpression to make the case that the PAR-1 kinase stands at the head of a temporally ordered series of tau phosphorylations.