Delineation of metabolic responses of Npc1^-/-nih mice lacking the cholesterol-esterifying enzyme SOAT2 to acute treatment with 2-hydroxypropyl-β-cyclodextrin.

ABSTRACT: Lipids present in lipoproteins cleared from the circulation are processed sequentially by three major proteins within the late endosomal/lysosomal (E/L) compartment of all cells: lysosomal acid lipase (LAL), Niemann-Pick (NPC) C2 and NPC1. When all three of these proteins are functioning normally, unesterified cholesterol (UC) exits the E/L compartment and is used in plasma membrane maintenance and various pathways in the endoplasmic reticulum including esterification by sterol O-acyltransferase 2 (SOAT2) or SOAT1 depending partly on cell type. Mutations in either NPC2 or NPC1 result in continual entrapment of UC and glycosphingolipids leading to neurodegeneration, pulmonary dysfunction, splenomegaly and liver damage. To date, the most effective agent for promoting release of entrapped UC

SUBMITTER: Ramirez CM 

PROVIDER: S-EPMC7680374 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature