HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An erratum has been published All Versions of this Article: M400411-JLR200v1 46/4/744    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kasperzyk, J. L. Articles by Seyfried, T. N. Search for Related Content PubMed PubMed Citation Articles by Kasperzyk, J. L. Articles by Seyfried, T. N. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 744-751, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice

J. L. Kasperzyk, A. d'Azzo, F. M. Platt, J. Alroy and T. N. Seyfried¹

Department of Biology, Boston College, Chestnut Hill, MA 02467

¹ To whom correspondence should be addressed. e-mail: thomas.seyfried{at}bc.edu

II³NeuAc-GgOse₄Cer (GM1) gangliosidosis is an incurable lysosomal storage disease caused by a deficiency in acid ß-galactosidase (ß-gal), resulting in the accumulation of ganglioside GM1 and its asialo derivative GgOse₄Cer (GA1) in the central nervous system, primarily in the brain. In this study, we investigated the effects of N-butyldeoxygalacto-nojirimycin (N B-DGJ), an imino sugar that inhibits ganglioside biosynthesis, in normal C57BL/6J mice and in ß-gal knockout (ß-gal^–/–) mice from postnatal day 9 (p-9) to p-15. This is a period of active cerebellar development and central nervous system (CNS) myelinogenesis in the mouse and would be comparable to late-stage embryonic and early neonatal development in humans. N B-DGJ significantly reduced total ganglioside and GM1 content in cerebrum-brainstem (C-BS) and in cerebellum of normal and ß-gal^–/– mice. N B-DGJ had no adverse effects on body weight or C-BS/cerebellar weight, water content, or thickness of the external cerebellar granule cell layer. Sphingomyelin was increased in C-BS and cerebellum, but no changes were found for cerebroside (a myelin-enriched glycosphingolipid), neutral phospholipids, or GA1 in the treated mice.

Our findings indicate that the effects of N B-DGJ in the postnatal CNS are largely specific to gangliosides and suggest that N B-DGJ may be an effective early intervention therapy for GM1 gangliosidosis and other ganglioside storage disorders.

Supplementary key words N-butyldeoxygalactonojirimycin • II³ (NeuAc)₂-LacCer • II³NeuAc-GgOse₄Cer • asialo derivative • myelin • cerebrosides • granule cells • neurodegeneration

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Brunetti-Pierri, M. B. Bhattacharjee, Z. J. Wang, Zili Chu, D. A. Wenger, L. Potocki, J. Hunter, and F. Scaglia Brain Proton Magnetic Resonance Spectroscopy and Neuromuscular Pathology in a Patient With GM1 Gangliosidosis J Child Neurol, January 1, 2008; 23(1): 73 - 78. [Abstract] [PDF]

				B. Bembi, F. Marchetti, V. I. Guerci, G. Ciana, R. Addobbati, D. Grasso, R. Barone, R. Cariati, L. Fernandez-Guillen, T. Butters, et al. Substrate reduction therapy in the infantile form of Tay-Sachs disease Neurology, January 24, 2006; 66(2): 278 - 280. [Abstract] [Full Text] [PDF]