肌萎缩侧索硬化（amyotrophic lateral sclerosis，ALS）和额颞痴呆（frontotemporal dementia，FTD）是以选择性、进行性神经元死亡为主要特征的神经系统变性疾病，给社会和家庭带来沉重负担。越来越多的证据表明，ALS 与FTD 的临床表现、病理特征和遗传特征有所重叠。与单纯的ALS 或FTD 相比，ALS-FTD（ALS 合并FTD）的疾病进展速度更快，患者的生存期也更短。目前，尚未阐明ALS 和FTD 的发病机制。许多研究揭示，ALS 与FTD 存在共同的病理基础：神经系统残存的神经元及胶质细胞内存在反式激活应答DNA 结合蛋白43（transactivation response DNA-binding protein 43 kDa，TDP-43）阳性包涵体。研究发现，ALS 和FTD 患者中枢神经系统内的TDP-43 蛋白失去正常的细胞核定位，而在细胞质内聚集形成包涵体。由此推测，TDP-43 蛋白的核内转入机制缺陷导致其正常功能丢失及获得性神经毒性可能是ALS-FTD 发病的始动因素之一。本文对核质转运障碍在ALS-FTD 发病机制中的最新研究进展进行综述。

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases characterized by selective and progressive loss of neurons in the central nervous system, bring heavy burden to society and family. More and more evidences have shown that ALS and FTD overlap in clinical manifestations, pathological changes and genetic characters. Compared with ALS or FTD, ALS-FTD has faster disease progression and shorter survival time. At present, the etiology and pathogenesis of ALS and FTD are unclear. Many studies have revealed that there is a common pathological basis for ALS and FTD:
TDP-43 (transactivation response DNA-binding protein 43 kDa)-positive inclusion bodies exist in the remnant neurons and glial cells of the nervous system. Studies have shown that TDP-43 protein in the central nervous system of patients with ALS-FTD loses normal nuclear localization and aggregates in the cytoplasm to form inclusion bodies. It is speculated that the loss of normal function and acquired neurotoxicity of TDP-43 may be one of the initiating factors of ALS-FTD. This paper reviews the latest research progress in the pathogenesis of ALS-FTD.