circFKBP8(5S,6)-encoded protein modulates α-synuclein expression in SH- SY5Y cells

Parkinson’s disease (PD) is the second most common neurodegenerative disease globally, majorly characterized by the abnormal aggregation of α-synuclein. Recent studies suggest that circular RNAs (circRNAs), predominantly formed by the back-splicing of pre-mRNAs, and the proteins they encode are implicated in neurodegenerative diseases, yet the specific role of circular RNA-encoded proteins in PD is not well understood. This research explored the expression and function of circFKBP8(5S,6)-encoded protein (cFKBP8), which is a protein encoded by the circular RNA, circFKBP8(5S,6), in a cellular model of PD. To simulate neuronal stress, an in vitro PD model was created by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP⁺). The expression of cFKBP8 was assessed using immunofluorescence staining and quantitative real-time polymerase chain reaction (RT-qPCR). A notable increase in cFKBP8 expression was found in MPP⁺-treated cells compared to untreated controls. Interestingly, gain- and loss-of-function studies revealed that overexpressing cFKBP8 led to higher α-synuclein expression, while knocking down cFKBP8 significantly decreased α-synuclein levels in SH-SY5Y cells. Overall, these results indicate that cFKBP8 responds to neurotoxic stress in a cellular model of PD and can influence the expression of α-synuclein in neuronal cells, which highlights the emerging role of circRNA-derived proteins in α-synuclein biology, with potential implications for developing biomarkers and therapeutic strategies for PD.