IntroductionPeroxisomes are essential organelles for normal human development and vital physiological processes. One of their key roles is lipid metabolism, particularly the β-oxidation of very long-chain fatty acids (VLCFAs). Peroxisome disease, such as X-linked adrenoleukodystrophy (ALD), is genetic disorder with impaired peroxisome functions. The ALD patients accumulate VLCFA in blood due to the inability of VLCFA metabolism in peroxisomes. Although the accumulation of VLCFA is diagnostic hallmark of ALD and considered to involve in demyelination of neurological tissues, a characteristic symptom of ALD 1), the precise mechanisms underlying VLCFA-induced neuronal degeneration remain poorly understood. Recently, we developed a method for solubilizing VLCFAs by forming albumin complexes in aqueous medium 2–4), and clarified chain length-dependent toxicity of VLCFA 3). We also clarified that a decrease in cellular C18:1 is a critical event in VLCFA-induced cytotoxicity and that supplementation of C18:1 protects the cells from VLCFA-induced apoptosis in peroxisome-deficient Chinese Hamster Overy (CHO) cells 4). This finding led us to examine the effect of Lorenzo’s oil, a dietary mixture of C18:1 (oleic acid) and C22:1 (erucic acid), which was once considered a promising therapy for ALD 5). The aim of this study is to develop a medicinal oil for treatment of ALD. To this end, we elucidate the mechanism by which C18:1 exerts a protective effect against VLCFA-induced apoptosis. We also investigated the effect of C22:1, a constituent of Lorenzo’s oil, on VLCFA-induced apoptosis in peroxisome-deficient CHO cells using our solubilization method.DemyelinationDevelopment of medicinal oil for treatment of adrenoleukodystrophyMD Hanif Ali2023. 4 ～ 2025. 3Tamotsu Tanaka, ProfessorGraduate School of Technology, Industrial and Social Science, Tokushima University― 265 ―
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