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PXD032670

PXD032670 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAmelioration of Pathologic -Synuclein-Induced Parkinson’s Disease by Irisin
DescriptionPhysical activity is thought to provide clinical benefit in Parkinson’s diseas (PD). Irisin is a blood-brain barrier permeable exercise-induced polypeptide secreted by muscle that mediates, in part, the beneficial effects of exercise. Here we show that irisin prevents pathologic -synuclein (-syn) induced neurodegeneration in the -syn preformed fibril mouse model of sporadic PD. Intravenous delivery of adenoviral irisin in vivo after the stereotaxic intrastriatal injection of -syn pre-formed fibrils reduced the formation of pathologic -syn and prevented the loss of dopamine neurons and reductions in striatal dopamine. Irisin also reduced the -syn pre-formed fibril induced motor deficits as assessed by the pole test and grip strength test. Administration of recombinant irisin in primary cortical neurons prevented pathologic -syn toxicity. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic -syn by enhancing endolysosomal degradation of pathologic -syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:14:33.245.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJonathan Van Vranken
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-20 15:35:03ID requested
12022-10-14 16:36:39announced
22023-11-14 08:14:35announced2023-11-14: Updated project metadata.
Publication List
Kam TI, Park H, Chou SC, Van Vranken JG, Mittenb, ü, hler MJ, Kim H, A M, Choi YR, Biswas D, Wang J, Shin Y, Loder A, Karuppagounder SS, Wrann CD, Dawson VL, Spiegelman BM, Dawson TM, -synuclein-induced Parkinson's disease by irisin. Proc Natl Acad Sci U S A, 119(36):e2204835119(2022) [pubmed]
Keyword List
submitter keyword: Irisin, alpha-synuclein, Neurodegeneration, Parkinson’s disease
Contact List
Bruce Spiegelman
contact affiliationDana Farber Cancer Institute, Boston, MA Harvard Medical School, Boston, MA
contact emailbruce_spiegelman@dfci.harvard.edu
lab head
Jonathan Van Vranken
contact affiliationHarvard Medical School
contact emailvan@hms.harvard.edu
dataset submitter
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Dataset FTP location
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