PXD012110

PXD012110 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of hippocampus and cerebral cortex in triple-transgenic mouse model of Alzheimer’s disease: Alterations with memantine treatment, part 2
Description	INTRODUCTION Alzheimer’s disease (AD) is an advanced neurodegenerative disorder characterized by progressive impairment in both memory loss and cognitive capacities, which resulting in severe dementia [1]. The pathogenesis of AD is complicated and poorly understood. According to the World Alzheimer Report 2018, it is estimated that AD affects at least 50 million persons throughout the world, and the number of people with AD will double nearly every 20 years [2]. Over the past decade, various theories have been developed for the neuropathological level of AD, but the most popular distinct pathological hallmarks is extracellular accumulation of amyloid beta (Aβ) plaques, as well as the neurofibrillary tangles (NFTs) composed of the hyperphosphorylated tau in the form of in the select brain regions [3]. The other factors including mitochondrial dysfunction, oxidative stress, brain inflammation and neurotransmitter disturbances pathology have been recognized as a contributing factor in the pathogenesis of AD [4]. To date, only symptomatic therapies are available for AD patients. Cholinesterase inhibitors (CIs) are approved for mild to moderate AD patients, and memantine is the only one N-methyl-D-aspartate receptor (NMDAR) antagonist has been approved for moderate to severe AD [5]. NMDAR is a glutamate ionotropic receptor, they display high Ca2+ permeability and voltage-dependent block by Mg2+[6]. In AD patients, NMDARs could be overactivated due to increasing glutamate release from presynaptic neurons. Overactived NMDARs lead first to Ca2+ overload in postsynaptic neurons, followed by desensitization and internalization, resulting in synaptic dysfunction and ultimately cell death [7, 8]. The numerous factors than can influence the levels of endogenous glutamate release in the pathogenesis of AD, deposition of Aβplaques, soluble Aβoligomers, NFTs, mitochondrial dysfunction and oxidative stress have been associated with the higher concentration of glutamate release[9, 10]. Memantine is an uncompetitive, moderate affinity NMDA receptor (NMDAR) antagonist which is used for a further therapeutic option of moderate to severe AD [5]. Its effects have been investigated in a large number of in vitro and in vivo studies, which indicated that memantine can against Aβ-induced glutamate-mediated toxicity, attenuate phosphorylation of tau and reduces level of total precursor protein (APP) in human neuroblastoma SK-N-SH cells [11], and lower Aβ1-42 secretion and plaques in primary cortical neuronal culture cells [9, 12]. Some studies showed that memantine also completely protected against Aβ-induced ROS injure in the primary hippocampal neurons [13]. Studies with transgenic animal models showed that memantine reduced the levels of soluble Aβ1-42, Aβ plaque deposition and lowered the loss of synaptic density in APP/PS1mice [4, 14, 15], and decreased the levels of total tau and hyperphosphorylated tau in 3×Tg-AD mice [3]. Furthermore, memantine altered genes expression in adult rat brain [16], and modulated protein profiles in Down syndrome mice brain [17]. However, no comprehensive study of proteomic characteristics description of 3×Tg-AD transgenic mice under the memantine treatment has been conducted to date as far as we searched. In order to better understand the multiple actions of memantine, we conducted detailed analysis of proteomics and bioinformatics to dissect the molecular mechanisms of memantine for the treatment of AD.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_13:40:03.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	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; deamidated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-19 02:10:17	ID requested
⏵ 1	2019-11-12 13:40:05	announced

Zhou X, Wang L, Xiao W, Su Z, Zheng C, Zhang Z, Wang Y, Xu B, Yang X, Hoi MPM, Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer's Disease. Exp Neurobiol, 28(3):390-403(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Alzheimer’s disease (AD), Memantine (MEM), Proteomics

Xinhua Zhou
contact affiliation	State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau 999078
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. PXD012110
     1. Label: PRIDE project
     2. Name: Proteomic profiling of hippocampus and cerebral cortex in triple-transgenic mouse model of Alzheimer’s disease: Alterations with memantine treatment, part 2