Human TBK1: A Gatekeeper of Neuroinflammation
Open accessAbstract
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.
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Genetic studies provide evidence that defects in autophagy predispose to amyotrophic lateral sclerosis.
“genetic studies have provided evidence that defects in autophagy predispose to ALS (156, 157).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [157]
In humans, rare gain-of-function mutations of TBK1 are associated with normal tension glaucoma and may affect autophagy and phagocytic functions of microglia.
“In human, rare gain-of-function mutations of TBK1 are associated with normal tension glaucoma. These mutations may affect autophagy and phagocytic functions of microglia (157).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [157]
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- Authors
- Ahmad, L., Zhang, S.-Y., Casanova, J.-L., & Sancho-Shimizu, V.
- Affiliations
- Imperial College London (GB)
- Inserm (FR)
- Hôpital Necker-Enfants Malades (FR)
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 22
- Issue
- 6
- Pages
- 511-527
- ISSN
- 1471-4914 (ISSN-L)
- PMC
- PMC4890605
- OpenAlex
- W2398211621
- Cited by
- 208
- References
- 122
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 23 · 2023: 22 · 2022: 21 · 2021: 27 · 2020: 25 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 4
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Agence Nationale de la Recherche (ANR-14-CE14-0008)
- National Institute of Allergy and Infectious Diseases (R01AI088364)
- National Institute of Neurological Disorders and Stroke (R01NS072381)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- TBK1, neuroinflammation, amyotrophic lateral sclerosis, frontotemporal dementia, normal-tension glaucoma, gain-of-function mutations, loss-of-function mutations, autophagy, inflammation
- MeSH terms
- Amyotrophic Lateral Sclerosis, Autophagy, Central Nervous System, Humans, Inflammation, Interferons, Mutation, Gene Expression, Protein Serine-Threonine Kinases, Disease Progression, Encephalitis, Herpes Simplex, Low Tension Glaucoma, Frontotemporal Dementia
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