The gangliosidoses: comparative features and research applications. Vet

Abstract. Ganglioside storage diseases are inherited defects of lysosomal hydrolases that result in intralysosomal accumulation of gangliosides and other complex metabolites. Gan-gliosidoses occur in man, cats, cattle, dogs and swine. In all species, these diseases are characterized clinically by relentlessly progressive neurological deterioration. Lysosomal hy-pertrophy with characteristic ultrastructural inclusions occur in neurons, endothelial and other cells. Definitive diagnosis requires biochemical identification of the storage product and enzyme deficiency. Gangliosidoses in animals are important models of human lysosomal diseases and may be a significant complication in the maintenance of certain purebred stocks of domestic animals. According to current concepts, the lysosomal system is the principal site of intracellular digestion and consists of membrane-bound cytoplasmic organelles con-taining more than 40 acid hydrolases capable of degrading most biologically impor-tant macromolecules. Mutations that cause reduced hydrolytic activity of lysosomal hydrolases result in diseases characterized by incomplete catabolism and concomitant accumulation (“storage”) of undergraded substrate within lysosomes [7, 9, 181