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Updated: Oct 3, 2025
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Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
Published on: May 16, 2017
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Emerging Connections between Nuclear Pore Complex Homeostasis and ALS
Sunandini Chandra1, C Patrick Lusk1
1Department of Cell Biology, Yale School of Medicine, 295 Congress Ave, New Haven, CT 06520, USA.
International Journal of Molecular Sciences
|February 15, 2022
Summary
Toxic RNA and proteins from the C9ORF72 gene disrupt nuclear transport in amyotrophic lateral sclerosis (ALS). Quality control at the nuclear envelope may offer new therapeutic targets for C9ORF72-linked ALS.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) involves motor neuron loss, with C9ORF72 gene expansions causing many familial cases.
- These expansions produce toxic RNA and dipeptide repeat (DPR) proteins that interfere with nuclear transport.
Purpose of the Study:
- To investigate how C9ORF72 repeat expansions alter nuclear pore complex (NPC) composition.
- To explore the role of nuclear envelope (NE) quality control pathways in C9ORF72-related ALS pathogenesis.
Main Methods:
- Analysis of NPC molecular composition in C9ORF72 model and patient neurons.
- Examination of NE surveillance pathways, including the role of CHMP7.
Main Results:
- C9ORF72 repeat expansions lead to changes in NPC structure and molecular makeup.
- Dysregulation of NE quality control pathways, mediated by proteins like CHMP7, is implicated in C9ORF72 ALS.
Conclusions:
- Nuclear envelope and NPC quality control mechanisms are critical in the C9ORF72 ALS pathological cascade.
- Understanding these pathways opens new avenues for therapeutic interventions in C9ORF72-linked ALS.
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