Objective: Parkinson’s disease (PD) is one of the increasing age-related diseases with no definite treatment. PD is considered as a disorder with genetic and non-genetic multi causative factors, in which perceptive the genetic connection is of paramount importance.

Background: In this study, employing concurrent in silico and in cellulo studies, some important genes involved in PD were investigated. Gene networks for PD were provided using DisGeNET, and the genes encoding proteins were selected and then the protein-protein interaction networks were determined. Using Cytohubba plugin, the most significant proteins involved in the selected interactions were chosen and their roles in the cellular pathways were investigated. The key proteins were selected using profiler database.

Method: In cellulo studies were explored using SHSY5Y dopaminergic cell lines to assess the obtained in silico results. To model PD, cells were exposed to pre-formed α-synuclein (αSN) amyloid aggregates. The pre-formed αSN aggregates in the presence of neobaicalein (a detoxified aggregates small molecule) was used also examined.

Results: The results showed that treatment with αSN significantly changed the expression of mTOR and GSK3β genes, and the presence of neobaicalein only affected mTOR. mTOR protein plays a key role in autophagy-related activities, while GSK3β gene is more involved in pathways related to oxidative stress and mitochondrial activity. More investigation is needed as to why the αSN inhibitor has a neutralizing effect on some genes.

Conclusion: The predicated pathways that were influenced by α-synuclein aggregates were proved by the biological experiments and the subjected small molecule which has effect on the fibrillation has impact on these pathways.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-the-network-of-genes-related-to-parkinsons-and-identification-of-key-proteins/