Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia

By A. Freischmidt, T. Wieland, Benjamin Richter, W. Ruf, V. Schaeffer, Kathrin Müller, Nicolai Marroquin, Frida Nordin, A. Hübers, P. Weydt and 30 more. 2015

743 citations recorded by the source corpus.

Subfields: Genetics, Neurology

How researchers see this paper

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In Neurology

1. Fiona M Menzies
2. Pegah Masrori
3. Koji Yamano
4. J. Harper
5. P. van Damme
6. N. Matsuda
7. Miyuki Sato
8. A. Ordureau

Citations in the corpus

• Amyotrophic lateral sclerosis: a clinical review (2020, background): “Mutations in TBK1 are most probably the fifth most common cause of autosomal dominant ALS, responsible for about 1% of patients [28,29] but up to 10% of patients with ALS-FTD [30].”
• Molecular mechanisms and physiological functions of mitophagy (2021, positive): “TBK1, which phosphorylates optineurin and enhances its binding to ubiquitin chains, is also mutated in ALS patients (Freischmidt et al , 2015; Oakes et al , 2017; Pozzi et al , 2017).”
• TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS (2020, background): “Interestingly, the adaptor protein downstream of STING, TBK1, is mutated and haploinsufficient in familial ALS (Cirulli et al., 2015; Freischmidt et al., 2015).”
• Deciphering the Molecular Signals of PINK1/Parkin Mitophagy. (2016, background): “Interestingly, mutations in TBK1 were also recently identified to cause ALS [53,54] while TBK1 gene duplications have been linked with glaucoma [55].”
• Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. (2017, positive): “Recently, mutations in TANKbinding kinase 1 (TBK1) have been associated with ALS (Cirulli et al., 2015; Freischmidt et al., 2015), TBK1 has been shown to phosphorylate OPTN to promote efficient mitophagy and p62 to allow autophagosome maturation (Moore and Holzbaur, 2015; Pilli et al, 2012).”
• The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of TBK1 activation and recruitment of OPTN and NDP52 to promote mitophagy (2015, background): “…amyotrophic lateral sclerosis (ALS) and that OPTN patient-derived mutants are defective in mitophagy implicates this arm of the autophagy system with this neurodegenerative disease (Cirulli et al., 2015; Fecto et al., 2011; Freischmidt et al., 2015; Maruyama et al., 2010; Wong and Holzbaur, 2014).”