The Hitchhiker's Guide to Nucleocytoplasmic Trafficking in Neurodegeneration.
Department
Neurobiology
Document Type
Article
Abstract
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.
Publication Date
6-1-2020
Publication Title
Neurochemical research
ISSN
1573-6903
Volume
45
Issue
6
First Page
1306
Last Page
1327
PubMed ID
32086712
Digital Object Identifier (DOI)
10.1007/s11064-020-02989-1
Recommended Citation
Moore, Stephen; Rabichow, Benjamin E; and Sattler, Rita, "The Hitchhiker's Guide to Nucleocytoplasmic Trafficking in Neurodegeneration." (2020). Translational Neuroscience. 488.
https://scholar.barrowneuro.org/neurobiology/488