Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia

J Clin Invest. 2017 Sep 1;127(9):3250-3258. doi: 10.1172/JCI90607. Epub 2017 Jul 24.


Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that is characterized by loss of motor neurons and shows clinical, pathological, and genetic overlap with frontotemporal dementia (FTD). Activated microglia are a universal feature of ALS/FTD pathology; however, their role in disease pathogenesis remains incompletely understood. The recent discovery that ORF 72 on chromosome 9 (C9orf72), the gene most commonly mutated in ALS/FTD, has an important role in myeloid cells opened the possibility that altered microglial function plays an active role in disease. This Review highlights the contribution of microglia to ALS/FTD pathogenesis, discusses the connection between autoimmunity and ALS/FTD, and explores the possibility that C9orf72 and other ALS/FTD genes may have a "dual effect" on both neuronal and myeloid cell function that could explain a shared propensity for altered systemic immunity and neurodegeneration.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Autoimmunity
  • C9orf72 Protein
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Frontotemporal Dementia / metabolism*
  • Frontotemporal Dementia / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation
  • Mice
  • Microglia / metabolism
  • Microglia / pathology*
  • Motor Neurons / metabolism
  • Mutation
  • Myeloid Cells / metabolism
  • Phenotype
  • Proteins / metabolism*
  • Superoxide Dismutase-1 / genetics


  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • Proteins
  • SOD1 protein, human
  • Superoxide Dismutase-1