副腎白質ジストロフィーの分子病態の解明と治療薬開発

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  • 守田 雅志
    富山大学大学院医学薬学研究部分子細胞機能学研究室

書誌事項

タイトル別名
  • Adrenoleukodystrophy: Molecular Pathogenesis and Development of Therapeutic Agents
  • フクジン ハクシツ ジストロフィー ノ ブンシ ビョウタイ ノ カイメイ ト チリョウヤク カイハツ

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  Adrenoleukodystrophy (ALD) is an inherited disorder characterized by progressive demyelination of the central nervous system and adrenal dysfunction. The biochemical characterization is made based on the accumulation of pathgnomonic amounts of saturated very long chain fatty acid (VLCFA, >22) in all tissues, including brain white matter and adrenal glands. The accumulation of VLCFA is linked to a mutation in the ABCD1 gene that encodes ABCD1/ALDP, a peroxisomal ABC protein. ABCD1/ALDP is thought to be involved in the active ATP-driven transport of VLCFA-CoA from the cytoplasm into the peroxisomes. However, the precise function of ABCD1/ALDP is still unclear. The accumulation of VLCFA is caused by reducing peroxisomal VLCFA β-oxidation and/or increasing fatty acid elongation. Since the reduction of accumulated VLCFA in the brain is thought to be crucial for preventing the progression of neurologic symptoms in X-ALD, compounds that can cross the blood-brain barrier and decrease the VLCFA levels in the brain would be a highly attractive candidate for effective treatment of ALD patients. We found that baicalein 5,6,7-trimethyl ether, a flavonoid derivative, decreased the VLCFA level in X-ALD fibroblasts, possibly by activating peroxisomal fatty acid β-oxidation. Continued pharmacologic studies of flavonoids and chemically modified derivatives may lead to major advances in the pharmacologic therapy for X-ALD.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 127 (7), 1059-1064, 2007-07-01

    公益社団法人 日本薬学会

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