Richard Magali, Arfi Audrey, Rhinn Hervé, Gandolphe Christelle, Scherman Daniel
Inserm U640, CNRS UMR 8151, Université Paris Descartes, Chemical and Genetic Pharmaceutical Laboratory, Ecole Nationale Supérieure de Chimie de Paris, Paris, France.
J Neurosci Res. 2008 Nov 15;86(15):3285-94. doi: 10.1002/jnr.21779.
Sly disease (MPS VII) is an autosomal-recessive lysosomal storage disorder resulting from beta-glucuronidase deficiency, which is characterized by a severe neurological impairment. MPS VII mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, thus appearing to be an excellent tool to delineate disease pathogenesis. The relationship between abnormal glycosaminoglycan storage and neurodysfunction is not yet well understood, but inflammatory components can be involved, as in several neurological lysosomal disorders. Inflammatory biomarkers are thus good candidates to evaluate the neurodegeneration state of the disease. By using quantitative polymerase chain reaction, we have compared the expression of selected genes of normal and MPS VII cerebral tissues, focusing on inflammation and apoptosis-related genes. The gene expression was evaluated in various brain regions throughout the lifetime of the animals. We have identified a specific expression profile for 27 genes, which was strongly marked in the central nervous system posterior region. Finally, new Sly disease markers were characterized that reflect neurological deterioration state, and that can be used in preclinical follow-up studies.
黏多糖贮积症VII型（Sly病）是一种常染色体隐性溶酶体贮积症，由β-葡萄糖醛酸酶缺乏引起，其特征为严重的神经功能损害。黏多糖贮积症VII型小鼠会累积未降解的糖胺聚糖，并模拟人类神经退行性疾病，因此似乎是阐明疾病发病机制的极佳工具。糖胺聚糖异常蓄积与神经功能障碍之间的关系尚未完全明确，但与其他几种神经溶酶体疾病一样，炎症成分可能参与其中。因此，炎症生物标志物是评估该疾病神经退行性变状态的良好候选指标。通过定量聚合酶链反应，我们比较了正常脑组织和黏多糖贮积症VII型脑组织中选定基因的表达，重点关注炎症和凋亡相关基因。在动物的整个生命周期内，对不同脑区的基因表达进行了评估。我们确定了27个基因的特定表达谱，该表达谱在中枢神经系统后部区域有明显特征。最后，鉴定出了反映神经功能恶化状态的新型Sly病标志物，可用于临床前随访研究。
