PXD056188

PXD056188 is an original dataset announced via ProteomeXchange.

Title	Proteomics of brain from a myeloid specific NPC1 KO mouse
Description	Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disorder mainly driven by mutations in NPC1 gene, causing lipid accumulation within late endosomes/lysosomes, and resulting in progressive neurodegeneration. Although microglial activation proceeds neuronal loss, it remains elusive whether loss of NPC1 in microglia actively contributes to NPC pathology. Here, we used a mouse model with depletion of NPC1 in myeloid cells to investigate the role of microglia in Niemann-Pick disease. In order to achieve the loss of NPC1 in myeloid cells, mice with floxed Npc1 alleles (Npc1 flox/flox) were crossed with mice expressing the constitutively active Cre recombinase under the myeloid-specific promotor of Cx3cr1. Hyperactive microglia initiated a pathological cascade resembling NPC-like phenotypes, including shortened lifespan, motor impairments, astrogliosis, neuroaxonal pathology and increased levels of neuronal injury biomarker NF-L. To study the differential vulnerability between the brain regions, we compared the cerebellar with the cerebral (brain without cerebellum) proteome in Cre- and Cre+ mice at late pathological stages. Our results suggest that microglial loss of NPC1 has profound effects on brain cell homeostasis especially in the cerebrum.
HostingRepository	PRIDE
AnnounceDate	2024-12-05
AnnouncementXML	Submission_2024-12-05_05:28:08.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-24 12:11:16	ID requested
⏵ 1	2024-12-05 05:28:08	announced

10.1126/SCITRANSLMED.ADL4616;

submitter keyword: cerebrum, brain,NPC1, cerebellum, mouse, microglia, Niemann-Pick disease type C

Dr. Stefan F. Lichtenthaler
contact affiliation	DZNE Munich, Neuroproteomics, Feodor-Lynen-Str. 17, 81377 München
contact email	stefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/12/PXD056188

PRIDE project URI

• PRIDE
  1. PXD056188
     1. Label: PRIDE project
     2. Name: Proteomics of brain from a myeloid specific NPC1 KO mouse