PXD010604

PXD010604 is an original dataset announced via ProteomeXchange.

Title	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
Description	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.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2018-12-04_03:57:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xinhua zhou
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-30 01:54:00	ID requested
1	2018-12-03 07:54:29	announced
⏵ 2	2018-12-04 03:57:40	announced	Updated project metadata.

Zhou X, Xiao W, Su Z, Cheng J, Zheng C, Zhang Z, Wang Y, Wang L, Xu B, Li S, Yang X, Pui Man Hoi M, Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment. J Proteome Res, 18(4):1542-1552(2019) [pubmed]

ProteomeXchange project tag: Human Brain Proteome Project (HUPO_HBPP) (B/D-HPP)

submitter keyword: Alzheimer’s disease (AD), Donepezil, Amyloid beta (Aβ), Proteomics, PINK1

Xinhua Zhou
contact affiliation	State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau
contact email	xinhuazhou9901@163.com
lab head
xinhua zhou
contact affiliation	University of Macau
contact email	xinhuazhou9901@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010604
     1. Label: PRIDE project
     2. Name: 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