The investigation of interaction and chaperon-like activity of α-synuclein as a protein in pathophysiology of Parkinson's disease upon direct interaction with tectorigenin.
Int J Biol Macromol
; 249: 125702, 2023 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-37414324
ABSTRACT
Analyzing the therapeutic potential of a therapeutic biomolecule requires an understanding of how it may interact with proteins and modify their corresponding functions. α-Synuclein is a protein which is widely involved in the pathogenesis of Parkinson's disease (PD) and shows chaperon-like activity. We have selected tectorigenin, a most common methoxyisoflavone extracted from plants, among therapeutic bioactive molecules that are documented to have different therapeutic effects. Herein, we aimed to explore how tectorigenin interacts with α-synuclein in vitro by mimicking the physiological environment. Spectroscopic as well as theoretical studies including molecular docking simulation, were used to examine the effects of tectorigenin on the conformation and dynamics of α-synuclein. It was shown that tectorigenin is able to quench the protein emission spectra relied on a mixed static-dynamic quenching mechanism. Furthermore, it was displayed that tectorigenin binding to α-synuclein leads to microenvironmental changes in the tertiary structure of protein, however the protein's secondary structure was almost unchanged. It was also deduced that tectorigenin results in thermal stability of α-synuclein structure, evidenced by less perturbation of α-synuclein secondary structure following elevation of temperature in the presence of tectorigenin relative to that of free form. Molecular docking simulation demonstrated that non-covalent reactions, mainly hydrogen bonds, had a key role in the interaction and stabilization of α-synuclein in the presence of tectorigenin. Moreover, chaperon-like activity of α-synuclein was improved in the presence of tectorigenin against two model proteins, ßL-crystallin and catalase. The findings showed that tectorigenin can lead to stabilization of α-synuclein, which may be used as a therapeutic agent in prevention of neurodegenerative diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Alfa-Sinucleína
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China