title: Human TBK1: A Gatekeeper of Neuroinflammation.
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.
authors.affiliation: Department of Virology, Division of Medicine, Imperial College London, Norfolk Place, London W2 1 PG, UK.
authors.forename: Liyana
authors.initials: L
authors.lastname: Ahmad
authors.affiliation: St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France; University of Paris Descartes, Imagine Institute, Paris, France.
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France; University of Paris Descartes, Imagine Institute, Paris, France; Howard Hughes Medical Institute, New York, NY, USA; Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, Paris, France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Department of Virology, Division of Medicine, Imperial College London, Norfolk Place, London W2 1 PG, UK; Department of Pediatrics, Division of Medicine, Imperial College London, Norfolk Place, London W2 1 PG, UK. Electronic address: v.sancho-shimizu@imperial.ac.uk.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho-Shimizu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001343:Autophagy; D002490:Central Nervous System / Q000378:metabolism*; D018450:Disease Progression; D020803:Encephalitis, Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057180:Frontotemporal Dementia / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D057066:Low Tension Glaucoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human
keywords: TBK1; amyotrophic lateral sclerosis; autophagy; dementia; glaucoma; herpes simplex encephalitis; interferon