The wide disparity in outcomes of Alzheimer's disease (AD) treatment from preclinical to clinical studies suggests an urgent need for more effective therapeutic targets and approaches to treat AD. CaMKII is a potential target for AD therapy; however, conflicting reports on the relationship between CaMKII and AD suggest a lack of deeper understanding of the interaction between CaMKII and AD. In addition to the lack of effective therapeutic targets, pharmacokinetic limitations of neuroprotective drugs, such as low lipophilicity to cross blood brain barrier, need to be urgently addressed in the practice of AD therapy. In this study, we prepared a carbon-based nanoparticle, Nano C60, and demonstrated that Nano C60 treatment promoted the translocation of phosphorylated CaMKIIα from the cytoplasm to the synapse in Aβ42 oligomers-treated cells and APP/PS1 mice. As a result, Nano C60 administration significantly improved spatial learning and memory in APP/PS1 mice. Our study suggests that synaptic-activated CaMKII may be more important than total CaMKII in AD treatment and provides a new strategy for AD therapy.
Keywords: Alzheimer’s disease; C60; CaMKII; hippocampus; nanoparticle; synaptic distribution.