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PXD039514

PXD039514 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEvaluation of therapeutic effects of tetramethylpyrazine nitrone in Alzheimer’s disease mouse model and proteomics analysis
DescriptionThe pathophysiology of Alzheimer’s disease (AD) is multifactorial with characteristic extracellular accumulation of amyloid-beta (Aβ) and intraneuronal aggregation of hyperphosphorylated tau in the brain. Development of disease-modifying treatment for AD has been challenging. Recent studies suggest that deleterious alterations in neurovascular cells happens in parallel with Aβ accumulation, inducing tau pathology and necroptosis. Therefore, therapies targeting cellular Aβ and tau pathologies may provide a more effective strategy of disease intervention. Tetramethylpyrazine nitrone (TBN) is a nitrone derivative of tetramethylpyrazine, an active ingredient from Ligusticum wallichii Franchat (Chuanxiong). We previously showed that TBN is a potent scavenger of free radicals with multi-targeted neuroprotective effects in rat and monkey models of ischemic stroke. The present study aimed to investigate the anti-AD properties of TBN. We employed AD-related cellular model (N2a/APPswe) and transgenic mouse model (3×Tg-AD mouse) for mechanistic and behavioral studies. Our results showed that TBN markedly improved cognitive functions and reduced Aβ and hyperphosphorylated tau levels in mouse model. Further investigation of the underlying mechanisms revealed that TBN promoted non amyloidogenic processing pathway of amyloid precursor protein (APP) in N2a/APPswe in vitro. Moreover, TBN preserved synapses from dendritic spine loss and upregulated synaptic protein expressions in 3×Tg-AD mice. Proteomic analysis of 3×Tg-AD mouse hippocampal and cortical tissues showed that TBN induced neuroprotective effects through modulating mitophagy, MAPK and mTOR pathways. In particular, TBN significantly upregulated PINK1, a key protein for mitochondrial homeostasis, implicating PINK1 as a potential therapeutic target for AD. In summary, TBN improved cognitive functions in AD-related mouse model, inhibited Aβ production and tau hyperphosphorylation, and rescued synaptic loss and neuronal damage. Multiple mechanisms underlie the anti-AD effects of TBN including the modulation of APP processing, mTOR signaling and PINK1-related mitophagy.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:45:26.222.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterxinhua zhou
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-17 01:18:45ID requested
12023-05-10 09:02:11announced
22023-11-14 08:46:00announced2023-11-14: Updated project metadata.
32024-10-22 05:45:29announced2024-10-22: Updated project metadata.
Publication List
Zhou X, Huang K, Wang Y, Zhang Z, Liu Y, Hou Q, Yang X, Hoi MPM, Evaluation of therapeutic effects of tetramethylpyrazine nitrone in Alzheimer's disease mouse model and proteomics analysis. Front Pharmacol, 14():1082602(2023) [pubmed]
10.3389/fphar.2023.1082602;
Keyword List
submitter keyword: Amyloid beta,Alzheimer’s disease, PINK1., Tetramethylpyrazine nitrone, Proteomic analysis
Contact List
Xinhua Zhou
contact affiliationGuangzhou Eighth People’s Hospital Guangzhou Medical University, Guangzhou, China.
contact emailxinhuazhou9901@163.com
lab head
xinhua zhou
contact affiliationUniversity of Macau
contact emailxinhuazhou9901@163.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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