Introduction: Parkinson's disease is one of the common neurodegenerative diseases among the elderly, one of the causes of this disease is aggregation and accumulation of alpha-synuclein protein. This protein is present in the nerve terminals of the brain, and if it aggregates and creates Lewy bodies, it causes the loss of dopaminergic neurons in the substantia nigra region of the brain and leads to the symptoms of Parkinson's disease. Recently, in order to improve Parkinson's disease, targeting this protein to inhibit its aggregation has been considered, and various inhibitors such as polyphenolic compounds, nanomaterials, etc. have been proposed. The bioluminescent system is used to analyze and report biological processes. This is due to high quantum efficiency and photon emission. Complementation of luciferase fragments is one of the techniques to investigate the interaction between proteins.
Methods: In this research, the effect of selected aromatic compounds on the aggregation of alpha-synuclein protein has been investigated using the split luciferase technique. The gene related to alpha-synuclein protein (A53T mutation) is connected to Nluc and Cluc gene fragments, and after expression, the reconstitution of luciferase activity was observed.
Results: In this research, 3 investigated compounds (A2, A3, A4) were individually affected after the transfection of the mentioned gene constructs on the HEK293T cell line. By examining the amount of luciferase activity after cell lysis, it was found that A3 has a significant effect on reducing the luciferase activity of the mentioned constructs and thus preventing the aggregation of alpha-synuclein protein.
Conclusion: Our findings suggest the need for further investigation on the capability of this aromatic compound in passing through the BBB and also on the effects of it on αS aggregation in animal models.
Keywords: parkinson disease, alpha-synuclein, protein aggregation, luciferase, aromatic compounds