McGoldrick Philip, Robertson Janice
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Front Cell Neurosci. 2023 Aug 31;17:1247297. doi: 10.3389/fncel.2023.1247297. eCollection 2023.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two adult-onset neurodegenerative diseases that are part of a common disease spectrum due to clinical, genetic, and pathological overlap. A prominent genetic factor contributing to both diseases is a hexanucleotide repeat expansion in a non-coding region of the gene. This mutation in leads to nuclear depletion and cytoplasmic aggregation of Tar DNA-RNA binding protein 43 (TDP-43). TDP-43 pathology is characteristic of the majority of ALS cases, irrespective of disease causation, and is present in ~50% of FTD cases. Defects in nucleocytoplasmic transport involving the nuclear pore complex, the Ran-GTPase cycle, and nuclear transport factors have been linked with the mislocalization of TDP-43. Here, we will explore and discuss the implications of these system abnormalities of nucleocytoplasmic transport in -ALS/FTD, as well as in other forms of familial and sporadic ALS.
肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）是两种成年起病的神经退行性疾病，由于临床、遗传和病理上的重叠，它们属于同一疾病谱。导致这两种疾病的一个重要遗传因素是该基因非编码区的六核苷酸重复扩增。该基因的这种突变导致Tar DNA-RNA结合蛋白43（TDP-43）的细胞核耗竭和细胞质聚集。TDP-43病理学是大多数ALS病例的特征，无论疾病病因如何，并且存在于约50%的FTD病例中。涉及核孔复合体、Ran-GTP酶循环和核转运因子的核质运输缺陷与TDP-43的错误定位有关。在这里，我们将探讨和讨论这些核质运输系统异常在ALS/FTD以及其他形式的家族性和散发性ALS中的影响。
