Proteomics

Dataset Information

38

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): TripleTOF 5600

ORGANISM(S): Mus musculus  

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: xinhua zhou  

LAB HEAD: Xinhua Zhou

PROVIDER: PXD010604 | Pride | 2018-12-03

REPOSITORIES: pride

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Publications

Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment.

Zhou Xinhua X   Xiao Wei W   Su Zhiyang Z   Cheng Jiehong J   Zheng Chengyou C   Zhang Zaijun Z   Wang Yuqiang Y   Wang Liang L   Xu Benhong B   Li Shupen S   Yang Xifei X   Pui Man Hoi Maggie M  

Journal of proteome research 20181207 4


Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3×Tg-AD). Mice (8-month old) were treated with done  ...[more]

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