Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatment Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatment

ABSTRACT: Donepezil, an acetylcholinesterase (AChE) inhibitor, was approved by FDA for the symptomatic therapies of patients with Alzheimer’s disease (AD) in 1996. Although donepezil have been regarded as the standard and first-line treatment for AD, the capacity of such drugs to alter the underlying disease process is still unclear. In this study, we sought to explore the possible protective mechanism of donepezil in triple-transgenic Alzheimer’s disease (3×Tg-AD) mice model. 3×Tg-AD mice were treated for 4 months with donepezil (1.3 mg /kg) and its effects were evaluated by behavioral tests and molecular analysis. The cognition of donepezil-treated mice was restored significantly. Reduced levels of soluble and insoluble amyloid beta 1-40 (Aβ 1-40) and amyloid beta 1-42 (Aβ 1-42) as well as senile plaques were observed. Moreover, donepezil treatment prevented the dendritic spine loss in hippocampus neurons. We further investigated the effects of donepezil on the hippocampal protein of 3×Tg-AD mice by quantitative proteomics technology. Proteomic results indicated that donepezil significantly elevated the levels of PINK1, NFASC, MYLK2, and RASN in the hippocampus, and modulated axon guidance, mitophagy, mTOR signaling, and MAPK pathway. The results suggested that donepezil induced neuroprotective effects through multiple mechanisms.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Hippocampal Neuron, Neutrophil

DISEASE(S): Alzheimer's Disease

SUBMITTER: xinhua zhou  

LAB HEAD: Xinhua Zhou

PROVIDER: PXD010604 | Pride | 2018-12-03

REPOSITORIES: Pride