PXD044499-1

PXD044499 is an original dataset announced via ProteomeXchange.

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_2023-09-07_19:22:49.875.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

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.

Dataset with its publication pending

submitter keyword: Irisin, Alzheimer's disease, Astrocytes, Neprilysin, ERK, STAT3

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

iProX dataset URI