2025年3月17日 / 最終更新日 : 2025年3月17日 ad_y ニュース

2025年 新着論文 6　分子生命科学分野から論文が発表されました

Graphene Quantum Dots Attenuate TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis

ACS Nano. 2025 Mar 11;19(9):8692-8710. doi: 10.1021/acsnano.4c15283. Epub 2025 Feb 4.

Authors

Na Young Park  1 , Yunseok Heo  2 , Ji Won Yang  1 , Je Min Yoo  3 , Hye Ji Jang  1 , Ju Hee Jo  1 , Su Jeong Park  1 , Yuxi Lin  2 , Joonhyeok Choi  2   4 , Hyeonjin Jeon  5 , Sun Joo Cha  5 , Gaeun Bae  6 , Donghoon Kim  1   7 , Juhee Kim  8 , Wade Zeno  8 , Jong Bo Park  9 , Noriyoshi Isozumi  10 , Tomohide Saio  11 , Seung Hyun Kim  12 , Hojae Lee  13 , Byung Hee Hong  6 , Minyeop Nahm  5 , Young-Ho Lee  2   14   15   16   17 , Young Bin Hong  1   18

Affiliations

  • 1 Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Korea.
  • 2 Biopharmaceutical Research Center, Korea Basic Science Institute, Cheongju 28119, Korea.
  • 3 Chaperone Ventures, LLC., Los Angeles, California 90006, United States.
  • 4 Chemical Analysis Team, Korea Basic Science Institute, Cheongju 28119, Korea.
  • 5 Dementia Research Group, Korea Brain Research Institute, Daegu 41062, Korea.
  • 6 Department of Chemistry and Advanced Institute of Convergence Technology, Seoul National University, Seoul 08826, Korea.
  • 7 Department of Pharmacology, College of Medicine, Dong-A University, Busan 49201, Korea.
  • 8 Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, United States.
  • 9 Graphene Square Chemical Inc., Pohang 37673, Korea.
  • 10 Department of Future Basic Medicine, Nara Medical University, Nara 634-8521, Japan.
  • 11 Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-0855, Japan.
  • 12 Department of Neurology, College of Medicine, Hanyang University, Seoul 04763, Korea.
  • 13 Biomanufacturing Center, Cedars-Sinai Medical Center, West Hollywood, California 90048, United States.
  • 14 Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Korea.
  • 15 Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea.
  • 16 Department of Systems Biotechnology, Chung-Ang University, Gyeonggi 17546, Korea.
  • 17 Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Miyagi 980-8578, Japan.
  • 18 Departments of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Korea.

Abstract

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.

Keywords: TDP-43; graphene quantum dots; liquid−liquid phase separation; stress granules.

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