AI Article Synopsis
- The article discusses how glycyrrhizic acid (GA) binds to α-synuclein, potentially aiding treatment for conditions known as synucleinopathies.
- GA inhibits the aggregation of α-synuclein and its neurotoxic effects through specific hydrogen bonds that form a complex structure, affecting the protein's stability.
- Experimental results indicate that GA's protective effects depend on its concentration, enhancing neural viability and reducing damage caused by α-synuclein aggregation through changes in the protein's structure.
Article Abstract
This article reveals the binding mechanism between glycyrrhizic acid (GA) and α-synuclein to may provide further information for the modulation of synucleinopathies using bioactive compounds. Therefore, the inhibitory activities of GA against α-synuclein aggregation and induced neurotoxicity were evaluated using different assays. Results showed that α-synuclein-GA binding was mediated by intermolecular hydrogen bonds leading to the formation of a slightly folded complex. Theoretical studies revealed that GA binds to the N-terminal domain of α-synuclein and triggers a compact structure around a major part of the N-terminal and the NAC regions along with fluctuations in the C-terminal domain, which are prerequisites for the inhibition of α-synuclein aggregation. Then, the cellular assays showed that GA as a potential small molecule can inhibit the oligomerization of α-synuclein and relevant neurotoxicity through modulation of neural viability, membrane leakage, and ROS formation in a concentration-dependent manner. As a result, the primary mechanism of GA's anti-aggregation and neuroprotective activities is the reorganized α-synuclein structure and fluctuating C-terminal domain, which promotes long-range transient intramolecular contacts between the N-terminal and the C-terminal domain.
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| http://dx.doi.org/10.1016/j.ijbiomac.2024.131423 | DOI Listing |
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