Human TBK1: A Gatekeeper of Neuroinflammation

Trends Mol Med. 2016 Jun;22(6):511-527. doi: 10.1016/j.molmed.2016.04.006.

Abstract

The importance of TANK binding kinase-1 (TBK1), a multimeric kinase that modulates inflammation and autophagy, in human health has been highlighted for the first time by the recent discoveries of mutations in TBK1 that underlie amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), normal tension glaucoma (NTG) or childhood herpes simplex encephalitis (HSE). Gain-of-function of TBK1 are associated with NTG, whereas loss-of-function mutations result in ALS/FTD or in HSE. In light of these new findings, we review the role of TBK1 in these seemingly unrelated, yet allelic diseases, and discuss the role of TBK1 in neuroinflammatory diseases. This discovery has the potential to significantly increase our understanding of the molecular basis of these poorly understood diseases.

Keywords: TBK1; amyotrophic lateral sclerosis; autophagy; dementia; glaucoma; herpes simplex encephalitis; interferon.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / immunology
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Autophagy
  • Central Nervous System / metabolism*
  • Disease Progression
  • Encephalitis, Herpes Simplex / genetics
  • Encephalitis, Herpes Simplex / immunology
  • Encephalitis, Herpes Simplex / metabolism*
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / metabolism*
  • Gene Expression
  • Humans
  • Inflammation / metabolism*
  • Interferons / immunology
  • Interferons / metabolism
  • Low Tension Glaucoma / genetics
  • Low Tension Glaucoma / immunology
  • Low Tension Glaucoma / metabolism*
  • Mutation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Interferons
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human