PXD019452

PXD019452 is an original dataset announced via ProteomeXchange.

Title	Proteomic signature of NPC1 KO microglia from conditional KO mice
Description	Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We demonstrate that microglial defects, including enhanced phagocytosis and impaired lipid trafficking, occur early in the NPC pathological cascade and precede neuronal death. Compromised microglial function during Npc1-/- mouse development is reflected by enhanced synaptic pruning and deficient turnover of myelin. Accumulation of the undigested myelin occurs mainly within multi-vesicular bodies (MVBs) of Npc1-/- microglia and not within lysosomes. This is in agreement with the impairments in recycling of myelin into lipid droplets. Macrophages of NPC patients displayed similar molecular and functional alterations as murine Npc1-/- microglia, strengthening the role of NPC1 in immune homeostasis. Generated ex vivo assays using patient macrophages are novel promising clinical tools to monitor the progression and therapeutic efficacy in NPC patients.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-13_08:27:30.881.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	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-28 07:05:38	ID requested
1	2021-03-04 12:33:55	announced
2	2024-10-22 05:18:40	announced	2024-10-22: Updated project metadata.
⏵ 3	2025-03-13 08:27:31	announced	2025-03-13: Updated project metadata.

10.1038/s41467-021-21428-5;

Colombo A, Dinkel L, M, ü, ller SA, Sebastian Monasor L, Schifferer M, Cantuti-Castelvetri L, K, ö, nig J, Vidatic L, Bremova-Ertl T, Lieberman AP, Hecimovic S, Simons M, Lichtenthaler SF, Strupp M, Schneider SA, Tahirovic S, Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia. Nat Commun, 12(1):1158(2021) [pubmed]

submitter keyword: Mouse, Niemann-Pick disease, microglia, neurodegeneration

Stefan F. Lichtenthaler
contact affiliation	DZNE Munich, Neuroproteomics, Feodor-Lynen Str. 17, 81377 Munich, Germany
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/2021/02/PXD019452

PRIDE project URI

• PRIDE
  1. PXD019452
     1. Label: PRIDE project
     2. Name: Proteomic signature of NPC1 KO microglia from conditional KO mice