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Transl. Neurodegener., Apr 16 2025, 14 (1) | https://doi.org/10.1186/s40035-025-00480-x
Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans
Kyung Hwan Park1, Euihyeon Yu1, Sooji Choi1, Sangyeong Kim1, Chanbin Park2,3, J. Eugene Lee2,3 and Kyung Won Kim1*
1Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, South Korea
2Biometrology Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science, Daejeon, South Korea
3Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, South Korea
*Correspondence: Kyung Won Kim
1Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, South Korea
2Biometrology Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science, Daejeon, South Korea
3Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, South Korea
*Correspondence: Kyung Won Kim
Abstract
Background: Cytoplasmic aggregation of TAR DNA binding protein 43 (TDP-43) in neurons is one of the hallmarks of TDP-43 proteinopathy. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are closely associated with TDP-43 proteinopathy; however, it remains uncertain whether TDP-43 aggregation initiates the pathology or is a consequence of it.
Methods: To demonstrate the pathology of TDP-43 aggregation, we applied the optoDroplet technique in Caenorhabditis elegans (C. elegans), which allows spatiotemporal modulation of TDP-43 phase separation and assembly.
Results: We demonstrate that optogenetically induced TDP-43 aggregates exhibited insolubility similar to that observed in TDP-43 proteinopathy. These aggregates increased the severity of neurodegeneration, particularly in GABAergic motor neurons, and exacerbated sensorimotor dysfunction in C. elegans.
Conclusions: We present an optogenetic C. elegans model of TDP-43 proteinopathy that provides insight into the neuropathological mechanisms of TDP-43 aggregates. Our model serves as a promising tool for identifying therapeutic targets for TDP-43 proteinopathy.
Methods: To demonstrate the pathology of TDP-43 aggregation, we applied the optoDroplet technique in Caenorhabditis elegans (C. elegans), which allows spatiotemporal modulation of TDP-43 phase separation and assembly.
Results: We demonstrate that optogenetically induced TDP-43 aggregates exhibited insolubility similar to that observed in TDP-43 proteinopathy. These aggregates increased the severity of neurodegeneration, particularly in GABAergic motor neurons, and exacerbated sensorimotor dysfunction in C. elegans.
Conclusions: We present an optogenetic C. elegans model of TDP-43 proteinopathy that provides insight into the neuropathological mechanisms of TDP-43 aggregates. Our model serves as a promising tool for identifying therapeutic targets for TDP-43 proteinopathy.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-17)
- 국내 연구진
- 생명과학 > 신경생물학
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