Advancements in TDP-43 research: Towards biomarkers and therapeutic targets for amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and premature death. Despite advances in understanding its pathology, ALS diagnosis and treatment remain primarily symptomatic, lacking dis...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
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| Series: | Aging and Health Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667032124000362 |
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| Summary: | Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and premature death. Despite advances in understanding its pathology, ALS diagnosis and treatment remain primarily symptomatic, lacking disease-specific biomarkers. TAR DNA-binding protein 43 (TDP-43) has emerged as a central player in ALS pathogenesis, undergoing pathological alterations including hyperphosphorylation, truncation, and cytoplasmic aggregation. This article reviews the physiological and pathological roles of TDP-43, its potential as a biomarker, and its candidacy as a therapeutic target. Challenges in detecting pathological forms of TDP-43 in biofluids hinder diagnostic advancements, yet recent research provides insights into its potential diagnostic and prognostic value. Moreover, ongoing efforts aim to develop targeted therapies, including genetic and proteostasis-based approaches, to mitigate TDP-43 pathology and its downstream effects. The article also discusses the need for novel animal models and antibodies to distinguish between pathological and physiological forms of TDP-43 for reliable biomarker development. Looking ahead, the article advocates for both linear and horizontal developments in TDP-43 research to advance ALS diagnosis, prognosis, and treatment paradigms. |
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| ISSN: | 2667-0321 |