Nano-Material-Based Therapeutic Strategy to Inhibit ALS-Causing Protein Aggregation

Research Summary

Most of patients with amyotrophic lateral sclerosis (ALS) exhibit a characteristic accumulation of aggregates formed by the TAR DNA-binding protein 43 (TDP-43) within neurons. In this study, our research team demonstrated that graphene quantum dots (GQDs), a type of nanomaterial, inhibit the liquid-liquid phase separation (LLPS) of TDP-43 and the formation of aggregates such as amyloid fibrils. In addition, GQDs were found to dissolve pre-formed aggregates, thereby reducing motor neuron damage and extending survival. By integrating protein science, biophysics, biochemistry, as well as cellular and animal experiments, we conducted a full-cycle and multidisciplinary investigation that yielded highly reliable results.

Expected Outcomes

The strategy of this study utilizing graphene quantum dots (GQDs) not only presents a new therapeutic possibility for amyotrophic lateral sclerosis (ALS), for which no definitive treatment currently exists, but also holds potential for application to various other diseases caused by protein aggregation.

Related Figures

• [Figure 1] Inhibition of Liquid–Liquid Phase Separation (LLPS) and Amyloid Fibril Formation of ALS-Causing TDP-43 by Graphene Quantum Dots (GQDs).
• [Figure 2] Administration of GQDs to ALS model mice resulted in delayed motor function decline through the inhibition of TDP-43 LLPS and aggregation, along with reduced motor neuron death and alleviation of neuroinflammatory responses.