This chapter describes storage disorders, defines the key pathogenic features affecting neurons in these diseases, and discusses the links between the storage disorders and known functions of the greater lysosomal system. The classification of lysosomal storage disorders can be based on their clinicopathological features or their defective proteins. The molecular causes of lysosomal storage disorders are far more complex than the simple absence of an individual lysosomal enzyme and include defects in a wide variety of soluble and transmembrane proteins, some of which lack any known enzyme activity. Neurons undergoing lysosomal storage, demonstrate the presence of abnormal storage bodies, principally in perikarya and in larger dendrites. Another area of speculation in terms of pathogenic mechanisms affecting neurons in storage diseases involves ganglioside distribution in diseased cells and the possibility that the endosomal-lysosomal (E/L) system defect leads to an abnormal distribution of specific glycosphingolipids (GSLs) in internal membranes of cells. Changes in the GSL constituents of intracellular membranes may be due to the catabolic defects inherent in lysosomal diseases. Two other mechanisms that are emerging as critical players in the development of neurological disease in storage disorders are apoptosis and inflammation.
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