PXD041850-1

PXD041850 is an original dataset announced via ProteomeXchange.

Title	Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration
Description	Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a critical determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.
HostingRepository	PRIDE
AnnounceDate	2023-05-17
AnnouncementXML	Submission_2023-05-17_06:46:22.177.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AndrewHowden
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-27 08:02:39	ID requested
⏵ 1	2023-05-17 06:46:22	announced
2	2024-10-22 05:45:46	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: central nervous system, NRF2, myelin, oligodendrocyte,astrocyte

Veronique E.Miron
contact affiliation	United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School, Edinburgh, UK, EH16 4TJ.
contact email	v.miron@ed.ac.uk
lab head
AndrewHowden
contact affiliation	University of Dundee
contact email	a.howden@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041850
     1. Label: PRIDE project
     2. Name: Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration