A therapy with miglustat, 2-hydroxypropyl-ß-cyclodextrin and allopregnanolone restores splenic cholesterol homeostasis in Niemann-pick disease type C1.
Lipids Health Dis
; 18(1): 146, 2019 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-31248418
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pregnanolona
/
Bazo
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1-Desoxinojirimicina
/
2-Hidroxipropil-beta-Ciclodextrina
Límite:
Animals
Idioma:
En
Revista:
Lipids Health Dis
Asunto de la revista:
BIOQUIMICA
/
METABOLISMO
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania