PXD044499
PXD044499 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Irisin reduces Amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling |
Description | A pathological hallmark of Alzheimer’s disease (AD) is the deposition of amyloid-β protein (Aβ) in the brain. Physical exercise has been shown to reduce Aβ burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin-domain III containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aβ pathology by increasing astrocytic release of the Aβ-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/β5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aβ. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aβ pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD. |
HostingRepository | iProX |
AnnounceDate | 2023-08-11 |
AnnouncementXML | Submission_2024-05-22_20:02:10.217.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eunhee Kim |
SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-08-10 21:58:53 | ID requested | |
1 | 2023-09-07 19:22:50 | announced | |
⏵ 2 | 2024-05-22 20:02:10 | announced | 2024-05-23: Update information. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Irisin, Alzheimer's disease, Astrocytes, Neprilysin, ERK, STAT3 |
Contact List
Se Hoon Choi | |
---|---|
contact affiliation | Massachusetts General Hospital |
contact email | choi.sehoon@mgh.harvard.edu |
lab head | |
Eunhee Kim | |
contact affiliation | Massachusetts General Hospital |
contact email | ekim43@mgh.harvard.edu |
dataset submitter |
Full Dataset Link List
iProX dataset URI |