METABOLISM OF COMPLEX LIPIDS OF NERVOUS TISSUES

神经组织复合脂质的代谢

• 批准号: 3860740
• 负责人: P G PENTCHEV
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3860740
• 关键词: HMG coA reductases; Niemann Pick disease; acyl coA; acyltransferase; cholesterol; enzyme biosynthesis; enzyme mechanism; esterification; heterozygote; homeostasis; human therapy evaluation; human tissue; inborn metabolism disorder diagnosis; intracellular transport; lipid metabolism; low density lipoprotein; molecular pathology; prenatal diagnosis; receptor; tissue /cell culture

The metabolic defect in patients with Types C and D Niemann-Pick disease has been shown to be due to abnormal intracellular cholesterol homeostasis. The molecular lesion in these disorders results in: (1) failure to down-regulate LDL receptors on cell membranes; (2) lack of down-regulation of HMGCoA reductase, a key enzyme in cholesterol biosynthesis; and (3) inability to up-regulate acyl cholesterol acyl CoA transferase. the enzyme that catalyzes the esterification of intracellular cholesterol. Tests have been developed and introduced into medical practice for the diagnosis of Types C and D Niemann-Pick disease and the identification of heterozygotes, and the prenatal diagnosis of these conditions. Current emphasis is on the development of effective therapy for patients with this novel metabolic disorder and the elucidation of its molecular basis.

C型和D型尼曼-皮克病患者的代谢缺陷 已被证明是由于细胞内胆固醇异常所致 体内平衡。 这些疾病中的分子损伤导致：(1) 未能下调细胞膜上的 LDL 受体； (2)缺乏 HMGCoA 还原酶（胆固醇中的关键酶）的下调 生物合成； (3) 无法上调酰基胆固醇酰基 CoA 转移酶。催化酯化反应的酶 细胞内胆固醇。 测试已开发并引入 C 型和 D 型尼曼-皮克病诊断的医疗实践 杂合子的鉴定和产前诊断 这些条件。 当前的重点是开发有效的 患有这种新型代谢性疾病的患者的治疗和 阐明其分子基础。