论文部分内容阅读
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。
Neuronal ceroid lipofuscinosis (NCLs) is a group of pediatric neurodegenerative diseases. Juvenile neuronal ceroid lipofuscinosis (JNCL) is one of them. Its clinical manifestations include retinal degeneration and further blindness, epilepsy and progressive cognitive and motor impairment. This article reviews its pathogenesis, including apoptosis, autophagy, plasma membrane-related dysfunction, obstruction of oxidative stress and NO transduction pathway, mitochondrial and lysosomal dysfunction, intracellular pH imbalance and so on. One of the most clearly studied is the two ways of apoptosis and autophagy. In apoptosis, defects in the normal function of the CLN3 gene lead to the accumulation of ceramide, resulting in increased mitochondrial membrane permeability (MMP) and ultimately the apoptosis that is dependent on caspases and not on caspases. Autophagy occurs both have been destroyed, the main reason for its destruction is the immature autophagic vesicles leading to autophagy can not be effectively recycled. This article describes the pathogenesis, especially its pathways of cell death, which will be helpful for the understanding of a class of neurodegenerative diseases such as JNCL.