Zhou X., et al. Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease and implication of PINK 1 regulation in donepezil treatment. Journal of Proteome Research. PMID: 30484658, 28/11/2018.
Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3xTg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Aβ1-40 and Aβ1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the nervous tissue showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3xTg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by western blotting.