Death associated protein kinase 1 (DAPK1) was initially discovered in the progress of gamma‐interferon induced programmed cell death, it is a key factor in the central nervous system, including Parkinson's disease (PD). However, the underlying mechanisms of DAPK1 in PD remain unclear and this research work aims to explore the potential mechanisms of DAPK1 in PD. In the study, we exposed SH‐SY5Y cells to MPP⁺ and treated mice with MPTP to investigate the roles of DAPK1 in PD and the underlying mechanisms. The results indicated that the expression of DAPK1 is significantly upregulated and negatively correlated with miR‐124‐3p levels in SH‐SY5Y cells treated by MPP⁺, and miR‐124‐3p mimics could effectively inhibit DAPK1 expressions and alleviate MPP⁺‐induced cell apoptosis. In addition, knockdown MALAT1 reduces the levels of DAPK1 and the ratio of SH‐SY5Y cell apoptosis, which is reversed via miR‐124‐3p inhibitor in vitro. Similarly, knockdown MALAT1 could improve behavioral changes and reduce apoptosis by miR‐124‐3p upregulation and DAPK1 downregulation in MPTP induced PD mice. Taken together, our data showed that lncRNA MALAT1 positively regulates DAPK1 expression by targeting miR‐124‐3p, and mediates cell apoptosis and motor disorders in PD. In summary, these results suggest that MALAT1/miR‐124‐3p /DAPK1 signaling cascade mediates cell apoptosis in vitro and in vivo, which may provide experimental evidence of developing potential therapeutic strategies for PD.

中文翻译：

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靶向 miR-124-3p 的 LncRNA MALAT1 调节 DAPK1 表达有助于帕金森病细胞凋亡

死亡相关蛋白激酶1（DAPK1）最初是在γ-干扰素诱导的程序性细胞死亡过程中发现的，它是中枢神经系统的关键因素，包括帕金森病（PD）。然而，DAPK1在PD中的潜在机制仍不清楚，本研究工作旨在探讨DAPK1在PD中的潜在机制。在该研究中，我们将 SH-SY5Y 细胞暴露于 MPP ⁺并用 MPTP 处理小鼠，以研究 DAPK1 在 PD 中的作用及其潜在机制。^{结果表明，MPP +}处理的SH-SY5Y细胞中DAPK1表达显着上调，且与miR-124-3p水平呈负相关，miR-124-3p模拟物能够有效抑制DAPK1表达，减轻MPP ⁺诱导的细胞凋亡。细胞凋亡。此外，敲低 MALAT1 会降低 DAPK1 的水平和 SH-SY5Y 细胞凋亡的比例，这一点在体外可通过 miR-124-3p 抑制剂逆转。同样，在 MPTP 诱导的 PD 小鼠中，敲低 MALAT1 可以通过 miR-124-3p 上调和 DAPK1 下调来改善行为变化并减少细胞凋亡。综上所述，我们的数据表明，lncRNA MALAT1 通过靶向 miR-124-3p 正向调节 DAPK1 表达，并介导 PD 中的细胞凋亡和运动障碍。总之，这些结果表明 MALAT1/miR-124-3p/DAPK1 信号级联在体外和体内介导细胞凋亡，这可能为开发 PD 潜在治疗策略提供实验证据。