Niccoli Teresa, Partridge Linda, Isaacs Adrian M
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, UCL, London WC1E 6BT, UK.
Hum Mol Genet. 2017 Oct 1;26(R2):R105-R113. doi: 10.1093/hmg/ddx247.
Like many other neurodegenerative diseases, age is a major risk factor in the development of ALS/FTD. But why is this the case? Recent genetic advances have highlighted some of pathways involved in the development of disease, and, strikingly, they appear to substantially overlap with those known to directly modulate the ageing process. Many ALS/FTD linked genes play a direct role in autophagy/lysosomal degradation, one of the most important pathways linked to ageing. However, systemic processes such as inflammation, as well as cellular maintenance pathways, including RNA splicing and nuclear-cytoplasmic transport have been increasingly linked both to disease and ageing. We highlight some of the shared mechanisms between the ageing process itself and emerging pathogenic mechanisms in ALS/FTD.
与许多其他神经退行性疾病一样，年龄是肌萎缩侧索硬化症/额颞叶痴呆（ALS/FTD）发病的主要风险因素。但为何会如此呢？近期的遗传学进展已凸显出一些与疾病发生相关的途径，而且，令人惊讶的是，它们似乎与那些已知直接调控衰老过程的途径有很大重叠。许多与ALS/FTD相关的基因在自噬/溶酶体降解中发挥直接作用，自噬/溶酶体降解是与衰老相关的最重要途径之一。然而，诸如炎症等全身过程以及包括RNA剪接和核质运输在内的细胞维持途径，已越来越多地与疾病和衰老联系在一起。我们着重介绍了衰老过程本身与ALS/FTD中新出现的致病机制之间的一些共同机制。
