Nucleocytoplasmic transport in C9orf72-mediated ALS/FTD

Ke Zhang; Jonathan C Grima; Jeffery D Rothstein; Thomas E Lloyd

doi:10.1080/19491034.2016.1172152

Nucleocytoplasmic transport in C9orf72-mediated ALS/FTD

Nucleus. 2016 Apr 25;7(2):132-7. doi: 10.1080/19491034.2016.1172152. Epub 2016 Apr 26.

Authors

Ke Zhang¹, Jonathan C Grima^{1

2}, Jeffery D Rothstein^{1

2

3}, Thomas E Lloyd^{1

2}

Affiliations

¹ a Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.
² b Department of Neuroscience, The Johns Hopkins University, Baltimore, MD, USA.
³ c The Brain Science Institute , The Johns Hopkins University , Baltimore , MD , USA.

Abstract

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.

Keywords: Amyotrophic Lateral Sclerosis (ALS); C9orf72; Frontotemporal Dementia (FTD); Nuclear Pore Complex (NPC); Nucleocytoplasmic transport; Ran GTPase; hexanucleotide repeat expansion (HRE).

Publication types

Review

MeSH terms

Active Transport, Cell Nucleus
Amyotrophic Lateral Sclerosis / complications*
Amyotrophic Lateral Sclerosis / metabolism*
Amyotrophic Lateral Sclerosis / pathology
Animals
C9orf72 Protein
Cell Nucleus / metabolism*
Frontotemporal Dementia / complications*
Humans
Protein Aggregates
Proteins / metabolism*

Substances

C9orf72 Protein
C9orf72 protein, human
Protein Aggregates
Proteins