Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses

Although the neuronal ceroid-lipofuscinoses (NCLs) are often referred to as lysosomal storage disorders, information on brain lysosomal hydrolases in NCLs is not available. We have determined the specific activities of several acid hydrolases in postmortem brain gray matter of infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) forms of NCL, patients affected with other neurological disorders (ON), and normal controls. The specific activities of beta-hexosaminidase A and B were significantly high in JNCL gray matter, whereas in LINCL, the increase is significant only in beta-hexosaminidase compared to the controls. A significant increase in the activities of alpha-mannosidase, beta-glucuronidase, and acid phosphatase was also observed in LINCL and JNCL patients compared to the control values. beta-galactosidase activity was also found to be elevated in JNCL brains over the controls. In contrast, activities of beta-glucosidase and sialidase appeared to be lowered in INCL and LINCL. On the other hand, alpha-fucosidase, beta-mannosidase, and sulfatase were unaffected in NCLs brains. Thus, the present data indicate NCLs related abnormalities in some of the acid hydrolases in brain gray matter, which are primarily glycoproteins of lysosomal origin. These data in conjuction with the reported association of sphingolipid activator proteins (SAP) A and D and lysosomal glycoproteins with NCL storage bodies imply abberations in the glycoconjugate metabolism and lysosomal function.