Gao Fen-Biao, Almeida Sandra, Lopez-Gonzalez Rodrigo
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
EMBO J. 2017 Oct 16;36(20):2931-2950. doi: 10.15252/embj.201797568. Epub 2017 Sep 15.
Frontotemporal dementia (FTD), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD overlaps extensively with the motor neuron disease amyotrophic lateral sclerosis (ALS), especially at the genetic level. Both FTD and ALS can be caused by many mutations in the same set of genes; the most prevalent of these mutations is a GGGGCC repeat expansion in the first intron of As shown by recent intensive studies, some key cellular pathways are dysregulated in the ALS-FTD spectrum disorder, including autophagy, nucleocytoplasmic transport, DNA damage repair, pre-mRNA splicing, stress granule dynamics, and others. These exciting advances reveal the complexity of the pathogenic mechanisms of FTD and ALS and suggest promising molecular targets for future therapeutic interventions in these devastating disorders.
额颞叶痴呆（FTD）是65岁以下人群中第二常见的痴呆形式，其特征是额叶和/或颞叶进行性萎缩。FTD与运动神经元疾病肌萎缩侧索硬化症（ALS）有广泛重叠，尤其是在基因层面。FTD和ALS都可能由同一组基因中的许多突变引起；这些突变中最常见的是C9orf72基因第一个内含子中的GGGGCC重复扩增。最近的深入研究表明，在ALS - FTD谱系障碍中，一些关键的细胞途径失调，包括自噬、核质运输、DNA损伤修复、前体mRNA剪接、应激颗粒动力学等。这些令人振奋的进展揭示了FTD和ALS致病机制的复杂性，并为这些毁灭性疾病未来的治疗干预提出了有前景的分子靶点。
