Amyotrophic lateral sclerosis (ALS) is a fatal late-onset neurodegenerative disease that specifically affects the function and survival of spinal and cortical motor neurons. ALS shares many genetic, clinical, and pathological characteristics with frontotemporal dementia (FTD), and these diseases are now recognized as presentations of a disease spectrum known as ALS/FTD. The molecular determinants of neuronal loss in ALS/FTD are still debated, but the recent discovery of nucleocytoplasmic transport defects as a common denominator of most if not all forms of ALS/FTD has dramatically changed our understanding of the pathogenic mechanisms of this disease. Loss of nuclear pores and nucleoporin aggregation, altered nuclear morphology, and impaired nuclear transport are some of the most prominent features that have been identified using a variety of animal, cellular, and human models of disease. Here, we review the experimental evidence linking nucleocytoplasmic transport defects to the pathogenesis of ALS/FTD and propose a unifying view on how these defects may lead to a vicious cycle that eventually causes neuronal death.

中文翻译：

---

核孔处的交通拥堵：所有道路均导致ALS / FTD中的核质运输缺陷。

肌萎缩性侧索硬化症（ALS）是一种致命的迟发性神经退行性疾病，特别影响脊髓和皮质运动神经元的功能和存活。ALS与​​额颞叶性痴呆（FTD）具有许多遗传，临床和病理学特征，这些疾病现在被认为是被称为ALS / FTD的疾病谱的表现。ALS / FTD中神经元丢失的分子决定因素仍在争论中，但是最近发现核质运输缺陷作为大多数（即使不是所有）形式的ALS / FTD的共同指标也极大地改变了我们对这种疾病的发病机理的理解。核孔的丧失和核孔蛋白的聚集，核形态的改变，使用各种动物，细胞和人类疾病模型已经发现，核运输受到损害和核运输受损是最突出的特征。在这里，我们审查了将核质运输缺陷与ALS / FTD的发病机理联系起来的实验证据，并就这些缺陷如何导致最终导致神经元死亡的恶性循环提出了统一的观点。