1999 Fiscal Year Final Research Report Summary
Research for the pathophysiology of adrenoleukodystrophy and therapeutic measures
| Project/Area Number |
10670588
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YAMADA Takeshi Kyushu University, Medical Science, Associate Professor, 大学院・医学系研究科, 助教授 (50230462)
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| Co-Investigator(Kenkyū-buntansha) |
TANIWAKI Takayuki Kyushu University, Medical Science, Lecturer, 大学院・医学系研究科, 講師 (80284496)
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| Project Period (FY) |
1998 – 1999
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| Keywords | adrenoleukodystrophy / knockout mouse / very long chain fatty acid / peroxisome / microglia / lovastatin / neural stem cell |
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| Research Abstract |
The pathophysiology of adrenoleukodystrophy (ALD) was investigated and the therapeutic measures for ALD was examined, using the ALD gene-knockout mice. The additional expression of very long chain acyl-CoA synthetase (VLACS) alone did not correct the impairment of β -oxidation of very long chain fatty acid (VLCFA) in ALD protein (ALDP)-deficient cells, suggesting that A+DP is required for VLCS to function. The amount of VLACS in the peroxisomal fraction was lowered in the ALDP-deficient mouse, suggesting that ALDP plays a role in the peroxisomal localization of VLACS.
The function of inflammatory cells was examined in the ALDP-deficient mouse. The ALDP-deficiency did not enhance the activation of microglia and macrophage by interferon-γ and lipopolysaccharide.
Lovastatin corrects the accumulation of VLCFA in the plasma of ALD patients, but did not that in the tissues including the brain and spinal cord of ALDP-deficient mice.
The murine neural stem cells, C17-2, was injected into the ventricle of the newborn ALDP-deficient mice. The accumulation of VLCFA was not corrected in the whole brain probably due to the small number of the implanted cells.
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Research Products
(7 results)
