PXD039514 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Evaluation of therapeutic effects of tetramethylpyrazine nitrone in Alzheimer’s disease mouse model and proteomics analysis |
| Description | The 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. |
| HostingRepository | PRIDE |
| AnnounceDate | 2024-10-22 |
| AnnouncementXML | Submission_2024-10-22_05:45:26.222.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 |
| Instrument | TripleTOF 5600 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2023-01-17 01:18:45 | ID requested | |
| 1 | 2023-05-10 09:02:11 | announced | |
| 2 | 2023-11-14 08:46:00 | announced | 2023-11-14: Updated project metadata. |
| ⏵ 3 | 2024-10-22 05:45:29 | announced | 2024-10-22: 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 affiliation | Guangzhou Eighth People’s Hospital Guangzhou Medical University, Guangzhou, China. |
| contact email | xinhuazhou9901@163.com |
| lab head | |
| xinhua zhou |
|---|
| contact affiliation | University of Macau |
| contact email | xinhuazhou9901@163.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039514
- Label: PRIDE project
- Name: Evaluation of therapeutic effects of tetramethylpyrazine nitrone in Alzheimer’s disease mouse model and proteomics analysis
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