Skip to main content
SpringerLink
Log in

Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses

  • Published:
Molecular and Chemical Neuropathology

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Annunziata P. and Federcio A. (1981) Brain glycosidase in Creutzfeldt-Jakob disease.J. Neurol. Sci. 49, 325–328.

    Article  PubMed  CAS  Google Scholar 

  • Armstrong D., Siakotos A., Koppang N., and Connole E. (1978) Studies on the retina and pigment epithelium in hereditary canine ceroid lipofuscinosis. 1. The distribution of enzymes in the whole retina and pigment epithelium.Invest. Ophthalmol. Vis. Sci. 17, 608–617.

    PubMed  CAS  Google Scholar 

  • 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 

  • Bayleran J., Hecktman P. and Saray W. (1984) Synthesis of 4-methylumbelliferyl-β-d-N-acetylglucosamine-6-sulfate and its use in classification of GM2 gangliosidosis genotypes.Clin Chim Acta 143, 73–89.

    Article  PubMed  CAS  Google Scholar 

  • Brady R. O., O’Brien J. H., Bradley, R. M., and Gal A. E. (1970) Sphingolipid hydrolases in brain tissue of patients with generalized gangliosidosis.Biochim. Biophys. Acta 210, 193–195.

    PubMed  CAS  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.

    CAS  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 

  • Ezaki J., Wolfe L. S., Higuti T., Ishidoh K., and Kominami E. (1995a) Specific delay of degradation of mitochondrial ATP synthase subunit c in late infantile neuronal lipofuscinosis (Batten disease).J. Neurochem. 64, 733–741.

    Article  PubMed  CAS  Google Scholar 

  • Ezaki J., Wolfe L. S., Ishidoh K., and Kominami E. (1995b) Abnormal degradative pathway of mitochondrial ATP in late infantile neuronal lipofuscinosis (Batten disease).Am. J. Med. Genet. 57, 254–259.

    Article  PubMed  CAS  Google Scholar 

  • Faisal Khan K. M., Brooks S. S., and Pullarkat R. K. (1995) Abnormal acid phosphatases in neuronal ceroid-lipofuscinoses.Am. J. Med. Genet. 57, 285–289.

    Article  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.

    PubMed  CAS  Google Scholar 

  • Furst W. and Sandhoff K. (1992) Activator proteins and topology of lysosomal sphingolipid catabolism.Biochim. Biophys. Acta 1126, 1–16.

    PubMed  CAS  Google Scholar 

  • Gieselmann V. (1995) Lysosomal storage diseases.Biochim. Biophys. Acta 1270, 103–136.

    PubMed  Google Scholar 

  • Hall N. A. and Patrick A. D. (1988) Accumulation of dolichol linked oligosaccharides in ceroid-lipofuscinosis (Batten disease).Am. J. Med. Genet. (Suppl).5, 221–232.

    Article  CAS  Google 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 

  • Haltia M., Rapola J., and Santavuori P. (1973) Infantile type of socalled neuronal ceroid-lipofuscinosis. Histological and electron microscopic studies.Acta Neuropathol. 26, 157–170.

    Article  PubMed  CAS  Google Scholar 

  • Hirsch H. E. (1968) Acid phosphatase localisation in individual neurons by quantitative histochemical method.J. Neurochem 15, 123–130.

    Article  PubMed  CAS  Google Scholar 

  • Hirsch H. E. (1969) Localisation of arylsulphatase in neurons.J. Neurochem. 16, 1147–1155.

    Article  PubMed  CAS  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.

    Article  PubMed  CAS  Google Scholar 

  • Kominami E., Ezaki J., Muno D., Ishido K., Ueno T., and Wolfe L. S. (1992) Specific storage of subunit c of mitochondrial ATP synthase in lysosomes of neuronal ceroid lipofuscinosis (Batten disease).J. Biochem 111, 278–282.

    PubMed  CAS  Google Scholar 

  • Krusius T., Viitala J., Palo J., And Maury C. P. J. (1986) Enrichment of high mannose-type glycans in nervous tissue glycoproteins in neuronal ceroidlipofuscinosis.J. Neurol. Sci. 72, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Mazurkiewicz J. E., Callahan L. M., Swash M., Martin J. E., and Messer A. (1993) Cytoplasmic inclusions in spinal neurons of the motor neuron degeneration (mnd) mouse.J. Neurol. Sci. 116, 59–66.

    Article  PubMed  CAS  Google Scholar 

  • Moroni-Rawson P., Palmer D. N., Jolly R. D., and Jordan T. W. (1995) Variant proteins in ovine ceroid-lipofuscinosis.Am. J. Med. Genet. 57, 279–284.

    Article  PubMed  CAS  Google Scholar 

  • Plum C. M. (1977) Acid phosphatase activity in lymphocytes from patients with Spielmeyer-Vogt-Batten’s syndrome.J. Clin. Chem. Clin. Biochem. 15, 645–648.

    PubMed  CAS  Google Scholar 

  • Pullarkat R. K. and Zawitosky S. E. (1993) Glycoconjugate abnormalities in the ceroid-lipofuscinoses.J. Inherited Metab. Dis. 16, 317–322.

    Article  PubMed  CAS  Google Scholar 

  • Pullarkat R. K., Kim K. S., Sklower S. L., and Patel V. M. (1988) Oligosaccharyl diphosphodolichols in the ceroid-lipofuscinoses.Am. J. Med. Gnet. (Suppl)5, 243–251.

    Article  CAS  Google Scholar 

  • Rider J. A. and Rider D. L. (1988) Batten disease: past, present and future.Am. J. Med. Genet. (Suppl)5, 21–26.

    Article  CAS  Google Scholar 

  • Sinha A. K. and Rose S. P. R. (1972) Compartmentation of lysosomes in neurons and neuropil and a new neuronal marker.Brain Res. 39, 181–196.

    Article  PubMed  CAS  Google Scholar 

  • Tyynela J., Baumann M., Henseler M., Sandhoff K., and Haltia M. (1995a) Sphingolipid activator proteins (SAPs) are stored together with glycosphingolipids in the infantile neuronal ceroid-lipofuscinosis.Am. J. Med. Genet. 57, 294–297.

    Article  PubMed  CAS  Google Scholar 

  • Tyynela J., Baumann M., Henseler M, Sandhoff K., and Haltia M. (1995b) Sphingolipid activator proteins in the neuronal ceroid-lipofuscinoses: an immunological study.Acta Neuropathol. 89, 391–398.

    Article  PubMed  CAS  Google Scholar 

  • Vesa J., Hellesten E., Verkruyse L. A., Camp L. A., Rapola J., Santavouri P., Hofmann S. L., and Peltonen L. (1995) Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis.Nature 376, 584–587.

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski K. E., Rapin I., and Heaney-Kieras J. (1988) Clinico-pathological variability in the childhood neuronal ceroid-lipofuscinoses and new observations on glycoprotein abnormalities.Am. J. Med. Genet. (Suppl)5, 27–46.

    Article  CAS  Google 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 

Download references

Author information

Authors and Affiliations

  1. New York State Institute for Basic Research in Developmental Disabilities, Department of Neurochemistry, New York State Office of Mental Retardation and Developmental Disabilities, 1050 Forest Hill Road, 10314, Staten Island, NY

    Vidudala V. T. S. Prasad & Raju K. Pullarkat

Authors
  1. Vidudala V. T. S. Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raju K. Pullarkat
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prasad, V.V.T.S., Pullarkat, R.K. Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses. Molecular and Chemical Neuropathology 29, 169–179 (1996). https://doi.org/10.1007/BF02815000

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02815000

Index Entries

Search

Navigation