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Neuron. 2017 Oct 11;96(2):285-297. doi: 10.1016/j.neuron.2017.07.029.

Lost in Transportation: Nucleocytoplasmic Transport Defects in ALS and Other Neurodegenerative Diseases.

Author information

1
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: jpaul.taylor@stjude.org.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord. The hallmark pathological feature in most cases of ALS is nuclear depletion and cytoplasmic accumulation of the protein TDP-43 in degenerating neurons. Consistent with this pattern of intracellular protein redistribution, impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to ALS pathology. Dysfunction in nucleocytoplasmic transport is also an emerging theme in physiological aging and other related neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. Here we review transport through the nuclear pore complex, pointing out vulnerabilities that may underlie ALS and potentially contribute to this and other age-related neurodegenerative diseases.

KEYWORDS:

ALS; C9ORF72; FTD; aging; dipeptide repeats; neurodegenerative diseases; nuclear pore; nucleocytoplasmic transport

PMID:
29024655
PMCID:
PMC5678982
DOI:
10.1016/j.neuron.2017.07.029
[Indexed for MEDLINE]
Free PMC Article

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