PXD024721

PXD024721 is an original dataset announced via ProteomeXchange.

Title	Tetrahydrocurcumin ameliorates Alzheimer's pathological phenotypes by inhibition of microglial cell cycle arrest and apoptosis via Ras/ERK signaling
Description	1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (tetrahydrocurcumin, THC) is a major bioactive metabolite of curcumin (the principal active ingredient of Curcuma longa L.), and overcomes the low bioavailability of curcumin, demonstrating the potential anti-inflammatory, antioxidant and neuroprotective properties, etc, some of which were considered to be even superior to curcumin. In the present study, the protective properties of THC in the hippocampus of APP/PS1 mice, and the effects of THC against Aβ-induced toxicity in BV-2 cells were explored. The data in vitro showed that Aβ induced decreased cell viability, and cell cycle arrest and apoptosis in BV-2 cells, which could be ameliorated by THC. In vivo, THC administration was able to rescue learning and memory, and reduce Aβ burden in the hippocampus of APP/PS1 mice. By comprehensive proteomic analysis of the hippocampus of mice, a total of 157 differentially expressed proteins were identified in APP/PS1 mice treated with THC (comparing with APP/PS1 mice), which were enriched in “T cell activation”, “lymphocyte proliferation” and “protein oligomerization”, etc. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the effects of THC on the cell cycle and apoptosis were mostly related to the “Ras signaling pathway” and “JAK−STAT signaling pathway”, etc. Using Western blot and ELISA, the down-regulation of Gab2 and K-Ras, and the up-regulation of caspase-3, TGF-β1 and TNF-ɑ were found in APP/PS1 mice. THC attenuated the abnormal expression of Gab2, K-Ras, caspase-3 and TNF-ɑ, and up-regulated Bag1 and TGF-β1 expression in APP/PS1 mice. In BV-2 cells, Aβ induced the down-regulation of Gab2, K-Ras and TGF-β1, and the overexpression of caspase-3, PARP1, cleaved-PARP1 and TNF-ɑ, which were markedly restored by THC. Moreover, THC up-regulated Bag1 expression in BV-2 cells treated with Aβ. The decreased transcriptional expression levels of Ccnd2 and Cdkn1a was also observed in Aβ-treated BV-2 cells. THC treatment alleviated down-regulation of Ccnd2, but did not affect the abnormal transcriptional expression of Cdkn1a caused by Aβ in BV-2 cells. For the first time, we identified that the action of THC in preventing AD was associated with inhibition of cell cycle arrest and apoptosis of microglia via the Ras/ERK signaling pathway, shedding new light on the role of THC in alleviating the progression of AD.
HostingRepository	PRIDE
AnnounceDate	2021-07-13
AnnouncementXML	Submission_2021-07-12_18:37:37.423.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu Xiao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker software

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-15 00:33:53	ID requested
⏵ 1	2021-07-12 18:37:37	announced

Dataset with its publication pending

submitter keyword: Tetrahydrocurcumin

microglia

cell cycle

cell apoptosis

Ras/ERK signaling pathway

Alzheimer’s disease

Yu Xiao
contact affiliation	Sichuan University; Chengdu University
contact email	11593652@qq.com
lab head
Yu Xiao
contact affiliation	Sichuan University;Chengdu university
contact email	11593652@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024721
     1. Label: PRIDE project
     2. Name: Tetrahydrocurcumin ameliorates Alzheimer's pathological phenotypes by inhibition of microglial cell cycle arrest and apoptosis via Ras/ERK signaling