C9ORF72 protein function and immune dysregulation in amyotrophic lateral sclerosis

Jesse D Lai; Justin K Ichida

doi:10.1016/j.neulet.2019.134523

C9ORF72 protein function and immune dysregulation in amyotrophic lateral sclerosis

Neurosci Lett. 2019 Nov 20:713:134523. doi: 10.1016/j.neulet.2019.134523. Epub 2019 Sep 27.

Authors

Jesse D Lai¹, Justin K Ichida²

Affiliations

¹ Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Neuroscience, Amgen Inc., Cambridge, MA, USA.
² Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: ichida@usc.edu.

PMID: 31568865
DOI: 10.1016/j.neulet.2019.134523

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing disease that affects upper and lower motor neurons eventually leading to paralysis and death by respiratory dysfunction. The most common genetic variant among ALS patients is a hexanucleotide repeat expansion within the first intron of the gene C9ORF72. This expansion elicits a complex cascade of events as a result of both gain- and loss-of-function mechanisms that contribute to neurodegeneration. Increasing evidence suggests that this repeat expansion in C9ORF72 also influences the immune homeostasis. In this review, we consolidate the current understanding of C9ORF72-mediated pathogenesis in both the central nervous system and peripheral immune system and propose mechanisms by which the immune system contributes to ALS.

Keywords: Amyotrophic lateral sclerosis; C9ORF72; Immunology; Neurodegeneration; Proteostasis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Amyotrophic Lateral Sclerosis / immunology*
Amyotrophic Lateral Sclerosis / physiopathology*
Animals
C9orf72 Protein / genetics
C9orf72 Protein / immunology*
C9orf72 Protein / physiology*
DNA Repeat Expansion
Humans
Nerve Degeneration / physiopathology*

Substances

C9orf72 Protein
C9orf72 protein, human