Cellular models of Batten disease.
Cellular models of Batten disease.
复制标题
巴顿病的细胞模型。
DOI：
10.1016/j.bbadis.2019.165559
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Minnis CJ
中科院分区：
文献类型：
--
作者：
Minnis CJ
神经元蜡质脂褐质沉积症 (NCL)，也称为 Batten 病，是一组由 13 个已知基因突变引起的神经退行性疾病。除一种 NCL 外，所有 NCL 均为常染色体隐性遗传，具有相似的病因，其特征是细胞溶酶体中自发荧光储存物质的积累。 NCL 的发病年龄和进展速度各不相同。它们总体上是最常见的溶酶体贮积病之一，但遗传上不同的疾病如何导致如此惊人相似的发病机制仍然是个谜。从细胞研究中我们已经了解到许多关于受影响基因编码的蛋白质的功能。此类研究利用了原始单细胞模型，例如含有基因直向同源物的酵母和阿米巴原虫、源自天然存在（绵羊）和基因工程（小鼠）动物模型的细胞或源自患者的细胞。最近，源自患者的诱导多能干细胞（iPSC）系已分化为神经细胞类型，以研究受疾病影响最严重的细胞的分子发病机制。在这里，我们回顾了细胞模型如何为 NCL 的生化理解提供信息，以及如何使用更复杂的模型来进一步加深这种理解，并可能作为未来治疗功效研究的平台。
The Neuronal Ceroid Lipofuscinoses (NCL), otherwise known as Batten disease, are a group of neurodegenerative diseases caused by mutations in 13 known genes. All except one NCL is autosomal recessive in inheritance, with similar aetiology and characterised by the accumulation of autofluorescent storage material in the lysosomes of cells. Age of onset and the rate of progression vary between the NCLs. They are collectively one of the most common lysosomal storage diseases, but the enigma remains of how genetically distinct diseases result in such remarkably similar pathogenesis. Much has been learnt from cellular studies about the function of the proteins encoded by the affected genes. Such research has utilised primitive unicellular models such as yeast and amoeba containing gene orthologues, cells derived from naturally occurring (sheep) and genetically engineered (mouse) animal models or patient-derived cells. Most recently, patient-derived induced pluripotent stem cell (iPSC) lines have been differentiated into neural cell-types to study molecular pathogenesis in the cells most profoundly affected by disease. Here, we review how cell models have informed much of the biochemical understanding of the NCLs and how more complex models are being used to further this understanding and potentially act as platforms for therapeutic efficacy studies in the future.