Dyrk1a Phosphorylation of α-Synuclein Mediating Apoptosis of Dopaminergic Neurons in Parkinson’s Disease

Objective. To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism mediating apoptosis PD. Methods. The protein level P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3β, PI3K, AKT, and cyclinD1 were detected. mRNA transcript levels DAT IL-1β, IL-6, COX-2, TNF-α Results. expressions decreased Dyrk1a-AAV-ShRNA ( P < 0.05), PI3K increased id="M2"> 0.05). Increased TH was shown id="M3"> group id="M4"> id="M5"> Dyrk1al-AAV-Sh-RNA id="M6"> Transcriptome sequencing showed that Fam220a, which expected activate STAT family binding activity participate negative regulation transcription through RNA polymerase II dephosphorylation differentially upregulated expression. untargeted metabolome major compounds hormones transmission mediators most metabolism-related pathways. Fam220a expression, expressed genes enriched for neuroactive ligand-receptor interaction, vascular smooth muscle contraction, melanogenesis-related Conclusion. Abnormal can affect modifications, dyrk1a knockdown activates PI3K/AKT pathway reduces dopaminergic neuron apoptosis. It provides a theoretical basis further mechanism.