Neuronal Death in Amyotrophic Lateral Sclerosis (ALS): What Can We Learn from Genetics?
Neuronal Death in Amyotrophic Lateral Sclerosis (ALS): What Can We Learn from Genetics?
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DOI：
10.2174/187152710791292558
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发表时间：
2010-07-01
影响因子：
3
通讯作者：
Sreedharan, J.
中科院分区：
文献类型：
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作者：
Sreedharan, J.
肌萎缩侧索硬化症（ALS）是一种难以研究的疾病，因为它大多是散发性的，并且进展迅速。导致家族性ALS（FALS）的基因的鉴定有助于促进我们对ALS发病机制的理解，最值得注意的是使用突变型超氧化物歧化酶1（SOD 1）疾病模型。15年来，SOD 1模型一直是ALS研究的支柱，但尚未开发出有效的治疗方法。然而，最近在ALS的遗传学方面取得了进展，鉴定了TAR DNA结合蛋白（TDP-43）的突变和肉瘤中的融合/脂肪肉瘤中的易位（FUS），这两者都在RNA加工和基因表达中发挥作用。ALS和额颞叶痴呆（FTD）之间的分子联系也被ALS-FTD与9号染色体的连锁所暗示。对散发性ALS（SALS）遗传学的研究成果较少，尽管随着我们进入重新测序时代，这可能会改变。关于ALS病因的进一步重要线索将来自于鉴定导致FALS的其他基因突变、增加对SALS易感性的变体以及改变ALS表型的遗传因素。
Amyotrophic lateral sclerosis (ALS) is a difficult disease to study as it is mostly sporadic and rapidly progressive. Identification of genes causing familial ALS (FALS) has been instrumental in advancing our understanding of ALS pathogenesis, most notably with the use of mutant superoxide dismutase 1 (SOD1) models of disease. For 15 years SOD1 models have been the backbone of ALS research, but no effective treatments have been developed. However, recent advances have been made in the genetics of ALS with the identification of mutations in TAR DNA binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), both of which have roles in RNA-processing and gene expression. Molecular links between ALS and frontotemporal dementia (FTD) are also suggested by linkage of ALS-FTD to chromosome 9. The study of the genetics of sporadic ALS (SALS) has been less fruitful, although this may change as we enter the era of resequencing. Further important clues as to the causes of ALS will come from the identification of other gene mutations that cause FALS, variants that increase susceptibility to SALS, and genetic factors that modify the ALS phenotype.