α-secretase–mediated processing of cellular prion protein and amyloid precursor protein is decreased in prion and Alzheimer's diseases. Mathéa Pietri et al. now show that activity of a kinase, PDK1, is increased in the brain following prion infection and with amyloid pathology. This results in internalization of TACE and impairs TACE-mediated α-secretase activity. Inhibition of PDK1 is beneficial in mouse models of prion infection and Alzheimer's disease, suggesting PDK1 may be targeted to attenuate disease progression.
- Mathéa Pietri
- Caroline Dakowski
- Benoit Schneider
