Exploration of novel phytochemicals as α-synuclein aggregation inhibitors in the context of Parkinson's disease therapy: an in-silico approach.

The misfolding and aggregation of alpha-synuclein play a pivotal role in the pathogenesis of Parkinson's disease (PD), contributing to neuronal dysfunction, the formation of Lewy bodies, and the manifestation of motor symptoms characteristic of PD. Understanding these molecular mechanisms is imperative for advancing therapeutic strategies for this neurodegenerative disorder. Current treatment modalities primarily involve dopamine replacement drugs, which fail to halt or slow disease progression. This study employs in-silico methods, including molecular docking and molecular dynamics simulations, to comprehensively evaluate naturally derived phytochemicals (n = 875) with neuroprotective or therapeutic potential in PD. Among these compounds, Crebanine exhibited the least binding energy at 13.7 kcal/mol, while Alpinetin showed -  3.2 kcal/mol. The RMSD values remained consistent after approximately 60 ns and 40 ns for Crebanine and Alpinetin, respectively, indicating stable predicted models. These findings underscore the potential of phytocompounds as candidates for PD therapeutics and warrant further in vitro and in vivo investigations to validate their efficacy. This approach represents a promising avenue for developing novel treatments that target the underlying molecular mechanisms of PD.