Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine
Farah Anjum1,2, Maram Jameel Hulbah1,2, Anas Shamsi3
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Life (Basel, Switzerland)
|November 27, 2025
Summary
TANK-binding kinase 1 (TBK1) mutations are linked to amyotrophic lateral sclerosis (ALS). Targeting TBK1 in autophagy and neuroinflammation pathways offers a promising therapeutic strategy for ALS and frontotemporal dementia (FTD).
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- * TANK-binding kinase 1 (TBK1) is a key genetic factor in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
- * TBK1 dysfunction impacts motor neuron health through autophagy, mitophagy, and immune regulation.
- * Understanding TBK1's structure is crucial for developing targeted therapies.
Purpose of the Study:
- * To review genetic and mechanistic links between TBK1 and ALS/FTD.
- * To highlight TBK1's roles in autophagy and neuroinflammation.
- * To summarize therapeutic strategies and challenges for TBK1 modulation.
Main Methods:
- * Synthesis of genetic and mechanistic evidence.
- * Review of structural biology data (conformations, inhibitor complexes).
- * Summary of structure-based and AI-assisted drug discovery approaches.
Main Results:
- * TBK1 variants are associated with ALS/FTD, implicating its role in pathogenesis.
- * TBK1 is central to autophagy and neuroinflammatory processes.
- * Advances in structure-based design and AI offer new therapeutic avenues.
Conclusions:
- * TBK1 is a significant therapeutic target for ALS/FTD.
- * Challenges include isoform selectivity, biomarker validation, and CNS delivery.
- * Integrating computational and experimental approaches may accelerate TBK1 modulator development.
