The widespread nature of nucleocytoplasmic trafficking defects and protein accumulation suggests distinct yet overlapping mechanisms in a variety of neurodegenerative diseases. Detailed understanding of the cellular pathways involved in nucleocytoplasmic transport and its dysregulation are essential for elucidating neurodegenerative pathogenesis and pinpointing potential areas for therapeutic intervention. The transport of cargos from the nucleus to the cytoplasm is generally regulated by the structure and function of the nuclear pore as well as the karyopherin α/β, importin, exportin, and mRNA export mechanisms. The disruption of these crucial transport mechanisms has been extensively described in the context of neurodegenerative diseases. One common theme in neurodegeneration is the cytoplasmic aggregation of proteins, including nuclear RNA binding proteins, repeat expansion associated gene products, and tau. These cytoplasmic aggregations are partly a consequence of failed nucleocytoplasmic transport machinery, but can also further disrupt transport, creating cyclical feed-forward mechanisms that exacerbate neurodegeneration. Here we describe the canonical mechanisms that regulate nucleocytoplasmic trafficking as well as how these mechanisms falter in neurodegenerative diseases.

中文翻译：

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《神经变性中核质质贩运的旅行者指南》。

核质运输缺陷和蛋白质积累的广泛性质表明在各种神经退行性疾病中截然不同但重叠的机制。对于阐明神经退行性发病机制和查明治疗干预的潜在领域，对参与核质运输及其失调的细胞途径的详细了解至关重要。货物从细胞核到细胞质的运输通常受核孔的结构和功能，以及核蛋白α/β，importin，exportin和mRNA出口机制的调节。在神经退行性疾病的背景下已广泛描述了这些关键转运机制的破坏。神经退行性变的一个常见主题是蛋白质的细胞质聚集，包括核RNA结合蛋白，重复扩增相关基因产物和tau。这些细胞质聚集部分是核细胞质运输机制失效的结果，但也可能进一步破坏运输，形成周期性的前馈机制，加剧神经变性。在这里，我们描述了规范核细胞质运输的规范机制，以及这些机制如何在神经退行性疾病中动摇。