Nucleocytoplasmic transport in C9orf72-mediated ALS/FTD.
A GGGGCC hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies indicate that disruption of nucleocytoplasmic transport pathways play a critical role in the pathogenesis of C9orf72-mediated ALS/FTD (C9-ALS). Here, we discuss mechanisms by which C9orf72 mutations cause nucleocytoplasmic transport deficits and contribute to disease pathogenesis. We review the current literature regarding nucleocytoplasmic transport disruption in C9-ALS, and discuss implications and directions for future research.
a Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.
Ke
K
Zhang
a Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.|b Department of Neuroscience, The Johns Hopkins University, Baltimore, MD, USA.
Jonathan C
JC
Grima
a Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.|b Department of Neuroscience, The Johns Hopkins University, Baltimore, MD, USA.|c The Brain Science Institute , The Johns Hopkins University , Baltimore , MD , USA.
Jeffery D
JD
Rothstein
a Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.|b Department of Neuroscience, The Johns Hopkins University, Baltimore, MD, USA.
Thomas E
TE
Lloyd
D021581:Active Transport, Cell Nucleus; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000073885:C9orf72 Protein; D002467:Cell Nucleus / Q000378:metabolism*; D057180:Frontotemporal Dementia / Q000150:complications*; D006801:Humans; D066329:Protein Aggregates; D011506:Proteins / Q000378:metabolism*
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D066329:Protein Aggregates; D011506:Proteins
Amyotrophic Lateral Sclerosis (ALS); C9orf72; Frontotemporal Dementia (FTD); Nuclear Pore Complex (NPC); Nucleocytoplasmic transport; Ran GTPase; hexanucleotide repeat expansion (HRE)