Graphene Quantum Dots Attenuate TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis
Aberrant phase separation- and stress granule (SG)-mediated cytosolic aggregation of TDP-43 in motor neurons is the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we found that graphene quantum dots (GQDs) potentially modulate TDP-43 aggregation during SG dynamics and phase separation. The intrinsically disordered region in the C-terminus of TDP-43 exhibited amyloid fibril formation; however, GQDs inhibited the formation of amyloid fibrils through direct intermolecular interactions with TDP-43. These effects were accompanied by attenuation of the ALS phenotype in animal models. Additionally, GQDs delayed the onset and survival of TDP-43 transgenic mouse models by enhancing motor neuron survival, reducing glial activation, and reducing the cytosolic aggregation of TDP-43 in motor neurons. In this research, we demonstrated the efficacy of GQDs on the SG-mediated aggregation of TDP-43 and the binding property of GQDs with TDP-43. Additionally, we demonstrated the clinical feasibility of GQDs using several animal models and other types of ALS caused by FUS and C9orf72. Therefore, GQDs could offer a new therapeutic approach for proteinopathy-associated ALS.
Authors
- Tomohide Saio (ORCID: https://orcid.org/0000-0003-3639-7399)
- Minyeop Nahm (ORCID: https://orcid.org/0000-0003-2195-4084)
- Jong Bo Park
- Joonhyeok Choi (ORCID: https://orcid.org/0000-0002-3800-0394)
- Gaeun Bae (ORCID: https://orcid.org/0009-0003-3688-3378)
- Je Min Yoo (ORCID: https://orcid.org/0000-0003-3074-859X)
- Hye Ji Jang
- Noriyoshi Isozumi (ORCID: https://orcid.org/0000-0002-2077-7576)
- Wade F. Zeno (ORCID: https://orcid.org/0000-0002-2341-8923)
- Ju Hee Jo
- Sun Hyung Joo (ORCID: https://orcid.org/0000-0002-5263-4617)
- Yuxi Lin (ORCID: https://orcid.org/0000-0002-5936-0954)
- Byung Hee Hong
- Su Jeong Park (ORCID: https://orcid.org/0000-0002-7589-7700)
- Yunseok Heo (ORCID: https://orcid.org/0000-0002-2233-4306)
- Donghoon Kim (ORCID: https://orcid.org/0000-0002-4111-5918)
- Seung Hyun Kim (ORCID: https://orcid.org/0000-0001-9644-9598)
- Ho-Jae Lee (ORCID: https://orcid.org/0000-0003-2170-355X)
- Ju-Hee Kim (ORCID: https://orcid.org/0000-0001-6380-0425)
- Young‐Ho Lee (ORCID: https://orcid.org/0000-0002-8441-5814)
- Young Bin Hong (ORCID: https://orcid.org/0000-0002-4333-3847)
- Ji Won Yang (ORCID: https://orcid.org/0000-0001-7629-6395)
- Na-Young Park (ORCID: https://orcid.org/0000-0002-4596-8491)
- Hyeonjin Jeon (ORCID: https://orcid.org/0000-0002-8206-2349)
Institutions
- University of Southern California (US)
- University of Science and Technology (YE)
- Cedars-Sinai Medical Center (US)
- Seoul National University (KR)
- Chungnam National University (KR)
- Tohoku University (JP)
- California Southern University (US)
- Applied Graphene Materials (United Kingdom) (GB)
- Chaperone Therapeutics (United States) (US)
- Nara Medical University Hospital (JP)
- Institute for Advanced Medical Research (US)
- Advanced Institute of Convergence Technology (KR)
- Dementia UK (GB)
- Korea Basic Science Institute (KR)
- Analytical Biosciences (China) (CN)
- Korea Brain Research Institute (KR)
- Japan Chemical Analysis Center (JP)
- Hanyang University (KR)
- Dong-A University (KR)
- Nara Medical University (JP)
- Chung-Ang University (KR)
- Korea University of Science and Technology (KR)
- Tokushima University (JP)
Publication Details
- Journal
- ACS Nano
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1021/acsnano.4c15283
- Citations
- 17
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 23.62