| Project/Area Number |
63570367
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KOBAYASHI Takuro Kyushu University, Faculty of Medicine Lecturer, 医学部, 講師 (40158902)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Leukodystrophy / Krabbe disease / metachromatic leukodystrophy / Psychosine / lysosulfatide / sphingosine / 白質変性症 / 異染性白質変性症 / GLD / MLD / 脱髄 |
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| Research Abstract |
Among several hereditary leukodystrophies, krabbe disease (GLD) is unique because of the absence of accumulation of a natural substrate of the deficient enzyme, galactosylceramide. We have recently demonstrated that the hydrolysis of galactosylceramide is catalyzed by two genetically distinct acid beta-galactosidases (galactosylceramidase I and II) and one of them (I) is deficient in GLD. Galactosylspingosine (psychosine) is a good substrate of galactosylceramidase I but not galactosylceramidase II. Svennerholm et al reported an accumulation of the lipid in the brain of GLD patients but the assay method was too complex and time-consuming. We developed a simple and sensitive assay method of galactosylspingosine using high-performance liquid chromatography, and demonstrated an abnormal accumulation of the lipid not only in the brain but also in somatic organs of human and murine cases of GLD. The tissue distribution of the accumulation and the cytotoxicity of galactosylspingosine strongly suggested the close relationship between the accumulation of galactosylsphingosine and demyelination seen in cases of GLD. Galactosylsphingosine was found to be synthesized from free spingoid bases by the catalysis of galactosyltransferase.
In metachromatic leukodystrophy (MLD), we found an abnormal accumulation of lysosulfatide. The accumulated amount was high in the cerebral white matter, spinal cord and peripheral nerve. The lipid was also so cytotoxic that accumulated lysosulfatide may cause demyelination in patients with MLD as in the case of GLD.
Further studies concerning toxic effects of these lyso-compounds to myelinforming cells (Schwann cells and oligodendrocytes) will be necessary.
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