entity

TBK1 loss

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TBK1 loss: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

1Connections

7Hypotheses

1Analyses

1Outgoing

0Incoming

4Experiments

3Debates

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Outgoing (1)

Target	Relation	Type	Str
cGAS-STING activation	causes	pathway	0.70

Incoming (0)

Source	Relation	Type	Str
No incoming edges

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TBK1 Loss Locks Microglia in an Aged/Senescent Transcription	0.878	ALS	What are the mechanisms by which microgl
TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimina	0.724	neurodegeneration	How do the seven novel ALS genes functio
TBK1 Loss Drives Motor Neuron Death Through Impaired Mitopha	0.531	ALS	What are the mechanisms by which microgl
TBK1 Loss Drives Microglial Senescence-SASP to Generate MMP-	0.499	ALS	What are the mechanisms by which microgl
TBK1 Loss Drives MMP-9-Mediated TDP-43 Fragmentation Through	0.376	ALS	What are the mechanisms by which microgl

TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagatio	0.000	ALS	What are the mechanisms by which microgl
TBK1 Loss Triggers eIF2α-Mediated Translational Repression T	0.000	ALS	What are the mechanisms by which microgl

Mentioning Analyses (1)

Scientific analyses that reference this entity

What are the mechanisms by which microglial senescence contributes to ALS pathol

neurodegeneration | 2026-04-26 | 12 hypotheses Top: 0.878

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Endothelium-specific TBK1 knockdown in atherosclerosis model	validation	atherosclerosis	0.900	endothelium-specific TBK1 knoc	proposed	N/A
TBK1-PAK1IP1-PAK1 signaling pathway analysis	exploratory	atherosclerosis	0.900	endothelial cells	proposed	N/A
GSK8612 treatment in atherosclerosis model	validation	atherosclerosis	0.800	atherosclerosis mouse model	proposed	N/A
LC-MS/Western blot analysis of TBK1 in atherosclerotic arteries	exploratory	atherosclerosis	0.800	mouse and human arteries with	proposed	N/A

Related Papers (17)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Autophagy and ALS: mechanistic insights and therapeutic implications. [PMID:34057020]	Chua JP, De Calbiac H, Kabashi E, Barmad	Autophagy	2022	2
Restricting intracellular Salmonella proliferation by coordinating p-TBK1 mediat [PMID:40660474]	Li J, Yang Y, Ge Y, Zhang X, Liu H et al	Autophagy	2026	0
Aberrant STING signalling promotes endothelial dysfunction and neurovascular inj [PMID:41419617]	Qin X, Chen S, Sun Y, Ma Z, Niu C et al.	Diabetologia	2026	0
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026	0
Dynamic regulation of TBK1 lactylation shapes antiviral immune responses. [PMID:41530535]	Xie Y, Zhang Y, Peng W, Zhang L, Hu Z et	Cell Mol Immunol	2026	0
RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodege [PMID:41603250]	Naumann M, Wierschin TM, Kretschmer S, D	Adv Sci (Weinh)	2026	0
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G e	Brain	2026	0
Systematic Review: Porphyromonas gingivalis Outer Membrane Vesicles From Pathoge [PMID:41980468]	Li Z, Luo C, Wen P, Zou T, Jin Z et al.	Int Dent J	2026	0
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026	0
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G,	Brain : a journal of neurology	2026	0
RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodege [PMID:41603250]	Naumann M, Wierschin TM, Kretschmer S, D	Advanced science (Weinheim, Ba	2026	0
Two FTD-ALS genes converge on the endosomal pathway to induce TDP-43 pathology a [PMID:36201573]	Unknown	Science	2022	0
Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-de [PMID:30643298]	Melamed Ze'ev; López-Erauskin Jone;	Nature neuroscience	2019	0
Reduction of matrix metalloproteinase 9 (MMP-9) protects motor neurons from TDP- [PMID:30458231]	Unknown	Neurobiology of disease	2019	0
Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-de [PMID:30643298]	Melamed Z, López-Erauskin J, Baughn MW,	Nature neuroscience	2019	0
TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and i [PMID:30146158]	Xu D, Jin T, Zhu H, Chen H, Ofengeim D,	Cell	2018	0
Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential thera [PMID:30127392]	Fujimori K, Ishikawa M, Otomo A, Atsuta	Nature medicine	2018	0

Debates (3)

Multi-agent debates referencing this entity

Debate: TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fu

closed · Rounds: 4 · Score: 0.33 · 2026-04-27

Investigate how microglial senescence drives ALS progression through inflammatio

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

What are the mechanisms by which microglial senescence contributes to ALS pathol

closed · Rounds: 6 · Score: 0.75 · 2026-04-26

Related Research

Hypotheses and analyses mentioning TBK1 loss in their description or question text

TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagation Through SASP-Media

Score: 0.000 · ALS · 2026-04-28

This hypothesis proposes that TBK1 loss-of-function mutations drive ALS pathogenesis by inducing senescence in astrocyte

TBK1 Loss Triggers eIF2α-Mediated Translational Repression Through Microglial SA

Score: 0.000 · ALS · 2026-04-28

This hypothesis proposes that TBK1 loss-of-function mutations drive ALS pathogenesis through a two-step mechanism: first