Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
DDX17 acts as a target of Buddlejasaponin IVb ameliorating dopaminergic neuron iron metabolism dysregulation in Parkinson's disease.
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Li Qiang-Ming, Zhu Man-Lei, Li Xiang, He Jing-Xing, Zha Xue-Qiang, Luo Jian-Ping, Zhang Feng-Yun
Аннотация
BACKGROUND: Identifying novel targets that ameliorating dopaminergic neuron iron metabolism dysregulation may provide potential therapeutic strategies for Parkinson's disease (PD). Buddlejasaponin IVb (BJP-IVb) is the first natural product that can ameliorate iron regulatory protein 2 (IRP2)-mediated iron metabolism dysregulation in dopaminergic neuron to suppress PD. BJP-IVb may exert this bioactivity through novel target. However, the pharmacological target of BJP-IVb is unclear.
PURPOSE: This study aimed to discovery the potential novel target of BJP-IVb ameliorating dopaminergic neuron iron metabolism dysregulation in PD.
METHOD: BJP-IVb probe (BJP-IVb-P) were synthesized to identify the potential novel target by affinity-based protein profiling. The expression of DEAD-box helicase 17 (DDX17) was knocked down in vitro and in vivo to prove the potential novel target of BJP-IVb is DDX17.
RESULTS: We proved that BJP-IVb could directly bind to DDX17. Dopaminergic neurons exhibit an elevated expression of DDX17 in PD. Dopaminergic neuron iron metabolism dysregulation and Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) signaling pathway activation in PD could be alleviated by the knockdown of DDX17 in vitro and in vivo. The inhibitory effect of BJP-IVb on dopaminergic neuron iron metabolism dysregulation and JAK2-STAT5 signaling pathway activation in PD could be abolished by the knockdown of DDX17 in vitro and in vivo.
CONCLUSION: This study first proved that DDX17 is a pharmacological target for ameliorating dopaminergic neuron iron metabolism dysregulation in PD, and BJP-IVb ameliorates dopaminergic neuron iron metabolism dysregulation by targeting DDX17.
PURPOSE: This study aimed to discovery the potential novel target of BJP-IVb ameliorating dopaminergic neuron iron metabolism dysregulation in PD.
METHOD: BJP-IVb probe (BJP-IVb-P) were synthesized to identify the potential novel target by affinity-based protein profiling. The expression of DEAD-box helicase 17 (DDX17) was knocked down in vitro and in vivo to prove the potential novel target of BJP-IVb is DDX17.
RESULTS: We proved that BJP-IVb could directly bind to DDX17. Dopaminergic neurons exhibit an elevated expression of DDX17 in PD. Dopaminergic neuron iron metabolism dysregulation and Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) signaling pathway activation in PD could be alleviated by the knockdown of DDX17 in vitro and in vivo. The inhibitory effect of BJP-IVb on dopaminergic neuron iron metabolism dysregulation and JAK2-STAT5 signaling pathway activation in PD could be abolished by the knockdown of DDX17 in vitro and in vivo.
CONCLUSION: This study first proved that DDX17 is a pharmacological target for ameliorating dopaminergic neuron iron metabolism dysregulation in PD, and BJP-IVb ameliorates dopaminergic neuron iron metabolism dysregulation by targeting DDX17.