Sphingolipidoses are a subgroup of
lysosomal storage diseases. They are defined as disorders caused by a genetic defect in catabolism of
sphingosine-containing
lipids. Catabolism of these
lipids involves
enzymes and activator
proteins. After the discovery of lysosomes by de Duve and the demonstration of the first defective lysosomal
enzyme by Hers in 1963, the first
enzyme deficiency for
sphingolipidoses was characterized in 1965 and all the defective
enzymes were demonstrated in the last three decades. In 1984, the first activator
protein was found and it expanded the concept of
sphingolipidoses. In the following years, many researches have been undertaken to understand the molecular basis of these diseases, the mechanism of pathogenesis, the mechanism of lysosomal digestion of
glycosphingolipids (GSLs) and the functional domains of lysosomal
enzymes. New hypotheses and theories have been put forward for the mechanism of lysosomal digestion and pathogenesis. However, although much has been done, the pathogenesis of
sphingolipidoses has not been fully elucidated. Mouse models of these diseases have facilitated the elucidation of pathogenesis and the development of therapeutic strategies for these diseases, which are not treatable at present except for Fabry and
type 1 Gaucher disease. The purpose of this review is to collect information on the recent researches related to
sphingolipidoses. The review includes the hydrolysis of GSLs in lysosome, mechanism of hydrolysis, pathogenesis and genetics of
sphingolipidoses, a brief mouse model and therapeutic strategies of these diseases.