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@MISC{Mller:279494,
author = {Müller, Stephan A and Lichtenthaler, Stefan},
title = {{D}ataset: {P}roteomics of brain from a myeloid specific
{NPC}1 {KO} mouse},
publisher = {PRoteomics IDEntifications Database},
reportid = {DZNE-2025-00821},
year = {2024},
abstract = {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.},
cin = {AG Lichtenthaler},
cid = {I:(DE-2719)1110006},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/279494},
}