همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Investigating the Potential of Natural Small Molecules as BDNF Mimetics for Neurodegenerative Disease Treatment: A Molecular Docking Study with TrkB Receptor

نویسندگان :

Sevil Babashpour¹ Dina Morshedi² Farhang Aliakbari³

1- 2National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran 2- 2National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran 3- 2National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

کلمات کلیدی :

BDNF Mimetics،Small Molecule،TrkB،Molecular Docking

چکیده :

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are characterized by the progressive degeneration of neurons and dysfunction of the nervous system. A major contributing factor in these diseases is the reduced level and activity of Brain-Derived Neurotrophic Factor (BDNF), a protein essential for neuronal survival, growth, and function. BDNF exerts its effects by binding to its primary receptor, TrkB, which triggers downstream signaling pathways that protect neurons from degeneration and enhance neuroplasticity. In neurodegenerative diseases, the diminished activity of BDNF contributes to neuronal apoptosis, impaired synaptic plasticity, and reduced cognitive function, making it a promising therapeutic target (Palasz & Wysocka, 2020; Colucci-D’Amato & Speranza, 2020). Given the critical role of BDNF in maintaining neuronal health, mimicking its neurotrophic effects through small molecules presents a novel and potentially effective therapeutic strategy (Kowiański & Lietzau1, 2018; Balakrishnan & Jannat, 2024). The objective of this study is to explore the potential of several natural small molecules as BDNF mimics by assessing their ability to activate the TrkB receptor. The molecules selected for investigation—Quercetin, Berberine, Baicalein, Oleuropein, Apigenin, Curcumin, and Resveratrol—are known for their antioxidant, anti-inflammatory, and neuroprotective properties. They have also demonstrated therapeutic promise in various in vitro and in vivo models of neurodegeneration (Aliakbari et al., 2018; Ma et al., 2014; Costa & Garrick, 2016; Schiavone & Trabace, 2018; Tian & Sharma, 2023). To simulate interactions between these compounds and the TrkB receptor, the 3D structure of the TrkB receptor (PDB ID: 1HCF) was retrieved from the Protein Data Bank (https://www.rcsb.org), and the structures of the small molecules were obtained from the PubChem database (https://pubchem.ncbi.nlm.nih.gov). The structures of these compounds —Quercetin (CID: 5280343), Berberine (CID: 2353), Baicalein (CID: 5281605), Oleuropein (CID: 5281544), Apigenin (CID: 5280443), Curcumin (CID: 969516), and Resveratrol (CID: 445154)—were optimized using VEGA ZZ software. The TrkB receptor structure was also prepared for docking using Swiss PDB Viewer and AutoDockTools (ADT, version 1.5.7). Molecular docking simulations were conducted with AutoDock Vina (version 1.1.2). The simulations allowed for the evaluation of docking scores, binding modes, and the stability of ligand-TrkB complexes (Scior, 2021). The results revealed that Quercetin, Berberine, and Baicalein exhibited the strongest binding affinities for the TrkB receptor among the compounds, with docking scores of -6.5 kcal/mol. Other interactions were observed between Oleuropein, Apigenin, Curcumin, and Resveratrol with the TrkB receptor, with docking scores of -6.3, -6.3, -5.7, and -5.6 kcal/mol, respectively. A docking score between -6.0 kcal/mol and -7.0 kcal/mol suggests moderate to strong binding affinity, indicating that these compounds may be good candidates for further investigation. In conclusion, these findings suggest that the natural compounds, particularly Quercetin, Berberine, and Baicalein, may mimic BDNF's action by activating the TrkB receptor, thereby providing neuroprotective effects. This study highlights the potential of natural small molecules as promising candidates for therapeutic development aimed at mimicking BDNF and providing neuroprotection in neurodegenerative diseases. The findings from this in silico study provide a strong foundation for further in vitro and in vivo studies to validate these results.

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