Inhibition of alpha-synuclein by plant extract

Inhibition of alpha-synuclein by plant extract
najmeh shadfar,^1,* nastaran rezaeepuor,²
Introduction: Parkinson is a progressive neurodegenerative disease caused by environmental and genetic factors which is known by motor symptoms including bradykinesia, resting tremor and movement rigidity. loss of dopamine secretion, and aggregation of α-synuclein are main causes of Parkinson disease symptoms. One of the genetic factors involved in the disease is the PARK1 gene, which is located on chromosome 4, and codes synuclein family protein. The misfolding and aggregation of the synuclein protein (α -syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson’s disease and other synucleinopathies. in addition, α-Synuclein may be the main component of the Lewy body in Parkinson's disease. Alpha-Synuclein is a small protein with 41 amino acids, which is free of friction in normal conditions. The protein is divided into three parts in terms of building characteristics. The middle part is hydrophobic and contains a highly repeatable sequence of glycine, proline, valine and alanine amines that plays a major role in the initiation of the pudding folding process. small molecules as a drug can be taken orally and are better at reaching different sites in the body. Our aim is to engineering herbal based ligand to inhibit a-syn aggregation.
Methods: Protein structure provided from Protein Data Bank with PDB access code of 4BXL. molecular docking methods explore the ligand conformations adopted within the binding sites of α-Synuclein as targets.in this study, autodock Vina under PyRX software as the virtual screening software was used and analysis of the absorption, distribution, metabolism and excretion properties (ADME) of virtual screening hits were studied by using FAF Drugs 4 web server. ligands were engineered using hyperchem software based on the structure of top hits retrieved from virtual screening process. New rationally designed ligands were then analyzed regarding ADME and toxicity to reach optimal scores.
Results: according to the information we were able to get the h-band from -6 to -9 and it is hypothesized that this drug can be used.
Conclusion: -
Keywords: alpha-synuclein -parkinson- neurodegenerative disease -Lewy body