Nervous system disease lysosomal storage diseases

Indications Central nervous system disease, lysosome storage disease, neurodegenerative disease, spinal cord injury Technology Stem-cell therapy... 

Primary lysosomal hydrolase defects. Two-thirds of the lysosomal storage diseases involve defects in genes that code for acid hydrolases. Table 41-2 lists 29 defects that have been defined so far. They have an autosomal recessive mode of inheritance, except for Hunter s syndrome and Fabry s disease, where the mode is X-linked recessive. The defective genes have been identified and mutations have been defined for nearly all. The nervous system is involved in most. Many of the disorders show a wide range of clinical severity, which may range from death in early childhood to a moderate disability in adulthood. 

Unlike lysosomal lipid-storage diseases (see below), very few metabolic diseases are known to be related to mutations of glycosyltransferases in ganglioside synthesis. The one new finding has been from that of Simpson et al. [45], who showed that a nonsense mutation of ST-I (GM3-synthase) is the cause of human autosomal recessive infantile-onset s)mptomatic epilepsy s)mdrome. Because ST-I is a key enz)me in the synthesis of all complex gangliosides, this report clearly indicates that the precise expression of complex gangliosides has critical biological functions in human nervous system development. 

There are multitudes of namrally occurring diseases of the central nervous system, including degenerative, traumatic, neoplastic, and metabolic disorders. Naturally occurring diseases for which there are potential models include models for include Parkinson s disease (PD), Huntington s disease (HD), Alzheimer s disease (AD), cerebral ischemia, miscellaneous neoplastic conditions, and lysosomal storage diseases. Examples of selected animal models of human disease will be briefly suimnarized. 

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