Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disorder due to mutations in NPC1 (95 % cases) or NPC2 genes, encoding NPC1 and NPC2 proteins, respectively. Both NPC1 and NPC2 proteins are involved in transport of intracellular cholesterol and their alteration leads to the accumulation of unesterified cholesterol and other lipids within the lysosomes. The disease is characterized by visceral, neurological and psychiatric symptoms. However, the pathogenic mechanisms that lead to the fatal neurodegeneration are still unclear. To date, several mutations leading to the generation of aberrant splicing variants or mRNA degradation in NPC1 and NPC2 genes have been reported. In addition, different lines of experimental evidence have highlighted the possible role of RNA-binding proteins and RNA-metabolism, in the onset and progression of many neurodegenerative disorders, that could explain NPC neurological features and in general, the disease pathogenesis. In this review, we will provide an overview of the impact of mRNA processing and metabolism on NPC disease pathology.

中文翻译：

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前RNA剪接缺陷和RNA结合蛋白参与Niemann Pick C型疾病。

Niemann-Pick C型（NPC）是一种常染色体隐性溶酶体贮积病，归因于分别编码NPC1和NPC2蛋白的NPC1（95％病例）或NPC2基因的突变。NPC1和NPC2蛋白均参与细胞内胆固醇的运输，其改变导致溶酶体内未酯化的胆固醇和其他脂质的积累。该疾病以内脏，神经和精神症状为特征。但是，导致致命性神经变性的致病机制仍不清楚。迄今为止，已经报道了几种突变，这些突变导致在NPC1和NPC2基因中产生异常的剪接变体或mRNA降解。此外，不同的实验证据都突显了RNA结合蛋白和RNA代谢的可能作用，在许多神经退行性疾病的发作和发展过程中，这可以解释NPC的神经系统特征，并通常可以解释疾病的发病机理。在这篇综述中，我们将概述mRNA加工和代谢对NPC疾病病理的影响。