Department of Economics and Food Sciences, University of Perugia, Via San Costanzo, 06126 Perugia, Italy.
Mol Neurobiol. 2012 Apr;45(2):247-57. doi: 10.1007/s12035-012-8248-y. Epub 2012 Mar 8.
Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by neurological impairment and blindness. NCLs are almost always due to single mutations in different genes (CLN1-CLN8). Ubiquitous accumulation of undigested material and of a hydrophobic inner mitochondrial membrane protein, the subunit c of mitochondrial ATP synthase, has been described. Although protein mutation(s) in the endoplasmic reticulum-lysosomes axis can modify the trafficking and the recycling of different molecules, one of the upstream targets in these diseases may be represented by the balance of gene expression. To understand if and how neurons modify the levels of important genes during the first phases of the disease, it is important to characterize the mechanisms of neurodegeneration. Due to the impossibility of performing this analysis in humans, alternative models of investigation are required. In this study, a mouse model of human NCL8, the mnd mouse has been employed. The mnd mice recapitulate many clinical and histopathological features described in NCL8 patients. In this study, we found an altered expression of different genes in both central and peripheral organs associated with lipopigment accumulation. This is a preliminary approach, which could also be of interest in providing new diagnostic tools for NCLs.
神经元蜡样脂褐质沉积症（NCLs）是一组以神经损伤和失明为特征的溶酶体贮积病。NCLs 几乎总是由于不同基因（CLN1-CLN8）的单一突变引起的。已经描述了未消化物质和疏水性线粒体膜内蛋白，即线粒体 ATP 合酶亚单位 c 的普遍积累。尽管内质网-溶酶体轴中的蛋白质突变可以改变不同分子的运输和循环，但这些疾病的上游靶点之一可能是基因表达的平衡。为了了解神经元在疾病的早期阶段是否以及如何改变重要基因的水平，了解神经退行性变的机制非常重要。由于不可能在人类中进行这种分析，因此需要替代的研究模型。在这项研究中，使用了一种人类 NCL8 的小鼠模型，即 mnd 小鼠。mnd 小鼠重现了 NCL8 患者中描述的许多临床和组织病理学特征。在这项研究中，我们发现与脂褐素积累相关的中枢和外周器官中不同基因的表达发生了改变。这是一种初步的方法，也可能为 NCLs 提供新的诊断工具。
