Graphene Quantum Dots Attenuate TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis
Source abstract
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.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Amyotrophic Lateral Sclerosis Research · Alzheimer's disease research and treatments · Prion Diseases and Protein Misfolding
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Translational Biomedical Sciences
Graduate School of Dong-A University
Biopharmaceutical Research Center
Korea Basic Science Institute
Chaperone Ventures, LLC.
Chemical Analysis Team
Dementia Research Group
Korea Brain Research Institute
Department of Chemistry and Advanced Institute of Convergence Technology
Seoul National University
Department of Pharmacology, College of Medicine
Dong-A University
Mork Family Department of Chemical Engineering and Materials Science
University of Southern California
Graphene Square Chemical Inc.
Department of Future Basic Medicine
Nara Medical University
Institute of Advanced Medical Sciences
Tokushima University
Department of Neurology, College of Medicine
Hanyang University
Biomanufacturing Center
Cedars-Sinai Medical Center
Bio-Analytical Science
University of Science and Technology
Funding
Korea Brain Research Institute · National Research Foundation of Korea · Korea Basic Science Institute
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