Neßlauer, Anna-Maria and Gläser, Anne and Gräler, Markus and Engelmann, Robby and Müller-Hilke, Brigitte and Frank, Marcus and Burstein, Christine and Rolfs, Arndt and Neidhardt, John and Wree, Andreas and Witt, Martin and Bräuer, Anja U. (2019) A therapy with miglustat, 2-hydroxypropyl-ß-cyclodextrin and allopregnanolone restores splenic cholesterol homeostasis in Niemann-pick disease type C1. Lipids in health and disease, 18. p. 146. ISSN 1476-511X

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Abstract BACKGROUND: Niemann-Pick disease type C1 (NPC1) is an autosomal-recessive lipid-storage disorder with an estimated minimal incidence of 1/120,000 live births. Besides other neuronal and visceral symptoms, NPC1 patients develop spleen dysfunction, isolated spleno- or hepatosplenomegaly and infections. The mechanisms of splenomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. METHODS: Here, we used an NPC1 mouse model to study a splenoprotective effect of a treatment with miglustat, 2-hydroxypropyl-ß-cyclodextrin and allopregnanolone and showed that this treatment has a positive effect on spleen morphology and lipid metabolism. RESULTS: Disease progress can be halted and blocked at the molecular level. Mutant Npc1 (Npc1-/-) mice showed increased spleen weight and increased lipid accumulation that could be avoided by our treatment. Also, FACS analyses showed that the increased number of splenic myeloid cells in Npc1-/- mice was normalized by the treatment. Treated Npc1-/- mice showed decreased numbers of cytotoxic T cells and increased numbers of T helper cells. CONCLUSIONS: In summary, the treatment promotes normal spleen morphology, stabilization of lipid homeostasis and blocking of inflammation, but alters the composition of T cell subtypes.

Item Type: Article
Uncontrolled Keywords: G-protein-coupling receptor; HPTLC; Lymphocyte; Niemann-pick disease type C1; PRGs; Phospholipids; S1P; Spleen; qRT-PCR
Subjects: Technology, medicine, applied sciences > Medicine and health
Divisions: Faculty of Medicine and Health Sciences > Department of Human Medicine
Date Deposited: 12 Mar 2020 11:24
Last Modified: 12 Mar 2020 11:24
URN: urn:nbn:de:gbv:715-oops-44410
DOI: 10.1186/s12944-019-1088-2

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