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 β-hexosaminidase A and B were significantly high in JNCL gray matter, whereas in LINCL, the increase is significant only in β-hexosaminidase compared to the controls. A significant increase in the activities of α-mannosidase, β-glucuronidase, and acid phosphatase was also observed in LINCL and JNCL patients compared to the control values. β-galactosidase activity was also found to be elevated in JNCL brains over the controls. In contrast, activities of β-glucosidase and sialidase appeared to be lowered in INCL and LINCL. On the other hand, α-fucosidase, β-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 conjunction 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.
Index EntriesNeuronal ceroid-lipofuscinoses Batten disease human brain hydrolases glycosidases β-hexosaminidase β-glucuronidase acid phosphatase
Unable to display preview. Download preview PDF.
- Barret A. J. and Heath M. F. (1977) Lysosomal enzymes, inLysosomes; a Laboratory Handbook (Dingle J. T., ed.), Elsevier, Amsterdam, pp. 20–145.Google Scholar
- Callen D. F., Baker E., Lane S., Nancarrow J., Thompson A., Whitemore S. A., MacLennan D. H., Berger R., Cherif D., Jarvela I., Peltonen L., Sutherland G. R. and Gardiner R. M. (1991) Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12.Am. J. Med. Genet. 49, 1372–1377.Google Scholar
- Conzelmann E. and Sandhoff K. (1987) Glycolipid and glycoprotein degradation, inAdvances in Enzymology, vol. 60. (Meister A., ed.), John Wiley, New York, pp. 90–216.Google Scholar
- Den Tandt W. R. and Hooghwinkel G. J. (1980) Brain lysosomal enzymes in generalized gangliosidosis and metachromatic leukodystrophy.Acta Neurol. 2, 10–14.Google Scholar
- Fearnley I. M., Walker J., Martinus R. D., Jolly R. D., Kirkland K. B., Shaw G. J., and Palmer D. N. (1990) The sequence of the major protein stored in ovine ceroid lipofuscinosis is identical with that of the dicyclohexylcarbodiimide-reactive proteolipid of mitochondrial ATP synthase.Biochem. J. 268, 751–758.PubMedGoogle Scholar
- Hall N. A., Lake B. D., Dewji N., and Patrick A. D. (1991) Lysosomal storage of subunit c of mitochondrial ATP synthase in Batten’s disease (Ceroidlipofuscinosis).Biochem. J. 275, 211–223.Google Scholar
- Jarvela I., Schleutker J., Haataja L., Santavuori P., Puhakka L., Manninen T., Palotie A., Sandkuijl L. A., Renlund M., White R., Aula P., and Peltonen L. (1991) Infantile form of neuronal ceroid-lipofuscinosis (CLN1) maps to the short arm of chromosome 1.Genomics 9, 170–173.PubMedCrossRefGoogle Scholar
- Zeman W. (1976) The neuronal ceroid-lipofuscinoses, inProgress Neuropathology, vol. 3 (Zimmermann H. M., ed.), Grune and Stratton, New York, pp. 203–223.Google Scholar
- Zeman W., Donahue S., Dyken P., and Green J. (1970) The neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome), inHandbook of Clinical Neurology, vol. 10,Leukodystrophies and Poliodystrophies, (Vinken P. J. and Bruyn G. W., eds.), North Holland Publishing Co., Amsterdam, pp. 588–679.Google Scholar