The mechanistic interaction, aggregation and neurotoxicity of α-synuclein after interaction with glycyrrhizic acid: Modulation of synucleinopathies.
Int J Biol Macromol
; 267(Pt 2): 131423, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38583832
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycyrrhizic Acid
/
Alpha-Synuclein
/
Protein Aggregates
/
Synucleinopathies
Limits:
Humans
Language:
En
Journal:
Int J Biol Macromol
Year:
2024
Document type:
Article
Affiliation country:
China