Lysosphingolipids and sphingolipidoses: Psychosine in Krabbe's disease.

摘要: Until recently, lipids were considered inert building blocks of cellular membranes. This changed three decades ago when found to regulate cell polarity and vesicle transport, the "lipid raft" concept took shape. The lipid-driven membrane anisotropy in form "rafts" that associate with proteins led view organized complexes various functions. Disturbance this organization can lead cellular, tissue, organ malfunction. Sphingolipidoses, lysosomal storage diseases are caused by enzyme deficiencies sphingolipid degradation pathway, be particularly detrimental brain. These result accumulation metabolites lysosomes, although it is not yet clear how affects Krabbe's disease (KD), or globoid leukodystrophy, was one first sphingolipidosis for which raft offered a potential mechanism. KD mutations β-galactocerebrosidase; however, elevation its substrate, galactosylceramide, observed detrimental. Instead, byproduct galactosylceramide metabolism, lysosphingolipid psychosine, accumulated. "psychosine hypothesis" has been refined showing psychosine disrupts lipid rafts vesicular transport critical function glia neurons. role an example disruption metabolism toxic lysosphingolipid, resulting neurotoxicity. © 2016 Wiley Periodicals, Inc.