Kallikrein-8 inhibition attenuates Alzheimer’s pathology in mice
Introduction</br> </br> Memory loss and increased anxiety are clinical hallmarks of Alzheimer's disease (AD). Kallikrein-8 is a protease implicated in memory acquisition and anxiety, and its mRNA is known to be up-regulated in AD-affected human hippocampus. Therefore, an involvement of Kallikrein-8 in Alzheimer's pathogenesis is conceivable but remains to be proved.</br> </br> Methods</br> </br> We determined the cerebral expression of Kallikrein-8 mRNA and protein during the course of AD in patients and in transgenic mice and tested the impact of Kallikrein-8 inhibition on AD-related pathology in mice and in primary glial cells. </br> </br> Results</br> </br> Kallikrein-8 mRNA and protein were up-regulated in both species at incipient stages of AD. Kallikrein-8 inhibition impeded amyloidogenic amyloid-precursor-protein processing, facilitated amyloid β (Aβ) clearance across the blood-brain-barrier, boosted autophagy, rAβ load and tau pathology, enhanced neuroplasticity, reversed molecular signatures of anxiety, and ultimately improved memory and reduced fear.</br> </br> Discussion</br> </br> Kallikrein-8 is a promising new therapeutic target against AD.
Use and reproduction:This work may be used under a
Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 License (CC BY-NC-ND 4.0)