Jude Uzoechina

Parkinson’s disease (PD) is the second most common neurodegenerative disease globally, characterized by the abnormal aggregation of α-synuclein. Recent studies suggest that circular RNAs (circRNAs), predominantly formed by back-splicing of pre-mRNAs, and the proteins they encode are implicated in neurodegenerative diseases; however, the specific role of circular RNA-encoded proteins in PD is understudied. This study investigated the expression and functional role of the circFKBP8(5S,6)-encoded protein (cFKBP8), translated from the circular RNA circFKBP8(5S,6), in a cellular model of PD. An in vitro PD model was created by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP⁺). cFKBP8 expression was assessed using immunofluorescence staining and quantitative real-time polymerase chain reaction (RT-qPCR). An increase in cFKBP8 expression was found in MPP⁺-treated cells compared to untreated controls. Functional analyses using Western blot revealed that cFKBP8 overexpression significantly increased α-synuclein expression. In contrast, silencing cFKBP8 decreased α-synuclein levels in SH-SY5Y cells. These results indicate that cFKBP8 expression is increased in a cellular model of PD and can influence α-synuclein expression in SH-SY5Y cells, thereby highlighting the role of circRNA-encoded proteins in α-synuclein biology, with potential implications for developing biomarkers and therapeutic strategies for PD. The online version contains supplementary material available at 10.1007/s11033-026-11723-z.

Circular RNAs (circRNAs) are structurally stable and covalently-linked ring RNA molecules. Due to backsplicing, they are directly joined by phosphodiester linkage, which confers much greater stability relative to their linear mRNA counterparts. Recent studies indicate that circRNAs also encode proteins involved in mechanisms associated with the pathogenesis of various diseases, offering new treatment insights. This review briefly summarizes the history, characteristics, and functions of circRNAs; the formation and translation mechanisms of circRNA-encoded proteins; and computational and experimental techniques for identifying/predicting the protein-encoding potential of circRNAs. We also summarized their role in disease pathogenesis, which includes how they could be targeted and harnessed as novel therapeutic options for disease treatment. Finally, we stated some current limitations to studies on circRNA-encoded proteins and concluded with a discussion of future research directions to facilitate effective clinical translation.