PXD034427

PXD034427 is an original dataset announced via ProteomeXchange.

Title	Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy and neuroinflammatory networks
Description	Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of Multiple Sclerosis (MS) symptoms, which has also shownbeneficial effects against Alzheimer’s (AD) and Parkinson’s (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling-based quantitative mass-spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was up-regulated while glycolysis and pentose phosphate pathway were down-regulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL-12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.
HostingRepository	PRIDE
AnnounceDate	2022-08-09
AnnouncementXML	Submission_2022-08-09_07:49:44.006.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mehdi Mirzaei
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; carbamoylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-09 14:12:03	ID requested
⏵ 1	2022-08-09 07:49:45	announced

Mirzaei M, Abyadeh M, Turner AJ, Wall RV, Chick JM, Paulo JA, Gupta VK, Basavarajappa D, Chitranshi N, Mirshahvaladi SSO, You Y, Fitzhenry MJ, Amirkhani A, Haynes PA, Klistorner A, Gupta V, Graham SL, Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks. Proteomics, 22(19-20):e2100247(2022) [pubmed]

submitter keyword: Fingolimod, Brain, Proteomics, Cerebellum, Frontal Cortex

Associate Professor Vivek Gupta
contact affiliation	Macquarie Medical School Macquarie University Australia Sydney 2109
contact email	vivek.gupta@mq.edu.au
lab head
Mehdi Mirzaei
contact affiliation	macquarie university
contact email	mehdi.mirzaei@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034427
     1. Label: PRIDE project
     2. Name: Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy and neuroinflammatory networks