Rationale: The synthetic sphingosine analog FTY720 is undergoing clinical trials as an immunomodulatory compound, acting primarily via sphingosine 1-phosphate receptor activation. Sphingolipid and cholesterol homeostasis are closely connected but whether FTY720 affects atherogenesis in humans is not known. Objective: We examined the effects of FTY720 on the processing of scavenged lipoprotein c...

So what does NPC1 really do? This is the key question. NPC1 shares significant structural homology with the resistance–nodulation–division (RND) family of permeases, members of which transport a number of substrates including heavy metals and lipids. Like its prokaryotic counterparts, NPC1 appears to transport fatty acids, but has not yet been shown to transport cholesterol. It has been suggest...

UNLABELLED Ebola virus (EBOV) causes hemorrhagic fevers with high mortality rates. During cellular entry, the virus is internalized by macropinocytosis and trafficked through endosomes until fusion between the viral and an endosomal membrane is triggered, releasing the RNA genome into the cytoplasm. We found that while macropinocytotic uptake of filamentous EBOV viruslike particles (VLPs) expre...

Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification s...

We report a 37-year-old woman with Niemann-Pick disease type C (NPC) 1. At the age of 8 years, she presented slow running followed by both fingers dystonia at the age of 10 years. At the age of 16 years, she developed declined scholastic achievement. On her first visit at the age of 17 years, she showed dystonia, ataxic gait and vertical supranuclear gaze palsy. We suspected it was NPC. She pre...

During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article inmBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real t...

The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER) is an important yet poorly understood cellular process. Niemann-Pick C1 (NPC1), a multi-pass integral membrane protein on the limiting membranes of late endosomes (LE)/lysosomes (Ly), is known to insert lumenal LDL-C to the limiting membrane o...

The Niemann-Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann-Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann-Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 gene. Both Niemann-...

Treatment for dyslipidemia in diabetes reduces cardiovascular events. Diabetes is associated with major abnormalities in fatty acid metabolism. The resulting disturbance results in an abnormal lipoprotein cascade from the large chylomicron through to the small HDL particle. This suggests that drugs that alter formation of the chylomicron particle might have a very important role in diabetic dys...