Neimann-Pick Disease type C is a hereditary lysosomal storagedisease due to mutations of the NPC1 or NPC2 genes. The productsof these genes encodes for components of a lysosomal machinerythat transport different kinds of lipids across the lysosomalmembrane. The main abnormalities of NPC1 de ciency phenotypeis the accumulation of free cholesterol (FC) and sphingolipids(GL) in brain, liver and other organs cells. Neurodegeneration andhepato-splenomegaly are common ndings. The NPC disease, inhis severe onset, leads to a precocious exitus, though the inhibitionof glyco-SL synthesis by miglustat has shown some clinicalbene t. Recently the physiopathological mechanism has beenpartly elucidated, being the rst step represented by the disruptionof lysosomal calcium homeostasis due to sphinganine accumulation.NPC1 Human skin broblasts (HSF) accumulate FC,as shown by lipin staining. The exact composition of the wholeNPC1-HSF lipidome is currently poor characterized. We developeda fully automated method to resolve individual lipids speciesfrom cells extracts by LC-ESI-MS in a Thermo Scienti c Q exactiveLC MS/MS apparatus. This methods allowed to obtain relativequanti cation and identi cation of more than ve hundreds ofdifferent compounds using both positive and negative ionizationmodes. We used this method to compare the lipidome pro lingof free living NPC-HSF with healthy control-HSF. Hopefully theresults will add useful information to support the understanding ofthe NPC pathophysiology.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2013|