Caspase-Mediated Truncation of Tau Potentiates Aggregation

Abstract EN

Caspase-mediated truncation of tau is associated with aggregation.

We examined the impact of manipulation of caspase activity on intracellular aggregation of a mutant form of tau (3PO) that forms spontaneous aggregates.

Treatment with the caspase inhibitor Z-VAD-fmk reduced both N and C-terminal tau truncation but did not significantly reduce aggregation.

Treatment with staurosporine, which activated caspases, increased C-terminal but not N-terminal truncation and enhanced aggregation.

These findings suggest that caspase activation is one potential route, rather than an obligatory initiation step, in aggregation, and that N- and C-terminal truncation contribute differentially to aggregation.