The molecular mechanisms of X-ALD pathology and the development of novel biomarker

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K11777
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Teikyo University
• Principal Investigator: Kotaro Hama 帝京大学, 薬学部, 准教授 (20534481)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 副腎白質ジストロフィー

Outline of Final Research Achievements

X-ALD is an inborn error of metabolism characterized by progressive neurological symptoms including demyelination and adrenal insufficiency. ABCD1 is crucial for very-long-chain fatty acids metabolism. However, the causal relationship and mechanism between the accumulation of very long-chain fatty acids and the clinical manifestations of X-ALD remain largely unknown. Furthermore, although X-ALD is caused by a single causative gene, its progression and clinical manifestations vary widely between each X-ALD patient, which hinders effective diagnosis and treatment of the disease. In the series of this study, we found an enzyme that is involved in the synthetic process of very long-chain fatty acid containing phospholipids. Also, a candidate metabolite that does not contain very long-chain fatty acids and accumulate in plasma from X-ALD patients. These observations contribute to clarify the molecular mechanisms of the X-ALD pathology as well as effective diagnosis of X-ALD.

Free Research Field

脂質

Academic Significance and Societal Importance of the Research Achievements

X-ALDでは極長鎖脂肪酸の蓄積が顕著であるが、極長鎖脂肪酸の蓄積がどのようにして脱髄や副腎機能の異常などに結びつくかという因果関係は殆ど明らかになっていない。本研究によって極長鎖脂肪酸の代謝機構の一端を担う候補分子が明らかになったことにより、極長鎖脂肪酸の病理的な意義を遺伝子（分子）の観点から解析することが可能になる。また、本研究ではX-ALD患者に蓄積する極長鎖脂肪酸以外のリン脂質分子種を見出した。このリン脂質分子種と臨床症状との相関性を明らかになれば、新規病態マーカーとして有用である可能性がある。