Cholesterol in Niemann-Pick Type C disease
Cholesterol in Niemann-Pick Type C disease
复制标题
DOI：
10.1007/978-90-481-8622-8_11
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Liao, Guanghong
中科院分区：
文献类型：
--
作者：
Bi, Xiaoning;Liao, Guanghong
尼曼-皮克C型（NPC）疾病与胆固醇和其他脂质在几乎每个器官的晚期内体/溶酶体中的积累有关;然而，神经变性是该疾病的致命原因。遗传分析已经确定NPC 1和NPC 2基因的功能缺失突变是该疾病的分子触发因素。虽然这些蛋白质的确切功能尚未阐明，但最近的研究表明，它们协调了晚期内体/溶酶体的胆固醇流出。NPC蛋白缺陷导致细胞内胆固醇运输受损和胆固醇生物合成失调。胆固醇稳态的破坏也与自噬活性的失调和早发性神经炎症有关，这可能有助于NPC疾病的发病机制。本章回顾了最近的成就，在调查的破坏胆固醇稳态诱导的神经退行性病变的NPC疾病，并提供了新的见解，为发展这种疾病的潜在治疗策略。
Niemann-Pick Type C (NPC) disease is associated with accumulation of cholesterol and other lipids in late endosomes/lysosomes in virtually every organ; however, neurodegeneration represents the fatal cause for the disease. Genetic analysis has identified loss-of-function mutations in NPC1 and NPC2 genes as the molecular triggers for the disease. Although the precise function of these proteins has not yet been clarified, recent research suggests that they orchestrate cholesterol efflux from late endosomes/lysosomes. NPC protein deficits result in impairment in intracellular cholesterol trafficking and dysregulation of cholesterol biosynthesis. Disruption of cholesterol homeostasis is also associated with deregulation of autophagic activity and early-onset neuroinflammation, which may contribute to the pathogenesis of NPC disease. This chapter reviews recent achievements in the investigation of disruption of cholesterol homeostasis-induced neurodegeneration in NPC disease, and provides new insight for developing a potential therapeutic strategy for this disorder.