青少年型神经元蜡样脂褐质沉积病(JNCL)的发病机制  

Mechanisms of juvenile neuronal ceroid lipofuscinosis(JNCL)

作　　者：王师尧[1] 金巍娜[1] 吴丹[1] 

机构地区：[1]北京大学医学部基础医学院医学遗传学系,北京100191

出　　处：《遗传》2009年第8期779-784,共6页Hereditas（Beijing)

基　　金：国家教育部博士点基金项目(编号:20070001801)资助

摘　　要：神经元蜡样脂褐质沉积病(Neuronal ceroid lipofuscinosis,NCLs)是一组儿科神经退行性变疾病,青少年型神经元蜡样脂褐质沉积病(Juvenile neuronal ceroid lipofuscinosis,JNCL)是其中一型。其临床表现包括视网膜退化进而失明、癫痫以及进行性的认知和运动能力的减退。本文综述了其发病机制,包括凋亡、自噬、质膜相关的功能障碍、氧化应激与NO转导通路受阻、线粒体和溶酶体功能障碍、胞内pH失衡等。其中研究最为清楚的是细胞凋亡和自噬两种方式。在凋亡中,CLN3基因正常功能的缺陷导致神经酰胺的积累,导致线粒体膜通透性增加(MMP),并最终引发依赖胱酰蛋白酶(Caspase)以及非依赖胱酰蛋白酶的凋亡。自噬既有发生又有被破坏,其破坏的主要原因是自噬小泡的不成熟导致自噬不能有效循环。本文对发病机制,尤其是其细胞死亡的途径的阐述,将有助于对JNCL等神经退行性病变一类疾病的认识。Juvenile neuronal ceroid lipofuscinosis （JNCL） is one type of the neuronal ceroid lipofuscinosis （NCLs）, which is a group of pediatric neurodegenerative disorders. The symptoms of JNCL are retinal degeneration （rd）, seizures, cognitive, and motor decline. The pathogenesis, summarized in this review, include apoptosis, autophagy, dysfunction in the structure associated with plasmalemma, oxidative stress and disruption of nitric oxide signaling, dysfunction of the mitochondrial and lysosome, unbalanced intracellular pH, and other relative mechanisms. Among them, only apoptosis and autophagy are well known. In apoptosis, the defects in CLN3 result in ceramide accumulation and upstream of mitochondrial membrane permeabilization, which eventually induce caspase-dependent and caspase-independent cell death. Autophagy exists but is disrupted because the immaturity of autophagic vacuoles leads to the failure of autophagy circulation. Understanding of the pathogenesis, especially the pathways of cell death in JNCL, is helpful to explore the mechanism of neurodegenerative disorders, such as JNCL.

关 键 词：青少年型神经元蜡样脂褐质沉积病 发病机制 细胞凋亡 自噬 

分 类 号：R748[医药卫生—神经病学与精神病学]