Parkinson’s disease (PD) seriously threatens human’s health. Researches have shown a close correlation between long non-coding RNAs (lncRNAs) and PD. However, the biological function of lncRNA homeobox transcript antisense RNA (HOTAIR) in PD remains largely unknown. In this study, we established PD models in vivo and in vitro by using 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP⁺) to assess the role of HOTAIR in pyroptotic cell death and neuronal damage. RNA immunoprecipitation (RIP) and dual luciferase reporter assay were used to verify the interaction between miR-326 and HOTAIR or ELAV like RNA binding protein 1 (ELAVL1). LncRNA HOTAIR was upregulated in PD mice and MPP⁺ induced SH-SY5Y cells. Additionally, knockdown of HOTAIR notably attenuated the symptom of PD in vivo. Downregulation of HOTAIR could obviously promoted cell viability and suppressed NLR family pyrin domain containing 3 (NLRP3) mediated pyroptotic cell death of SH-SY5Y cells in the presence of MPP⁺. Further, lncRNA HOTAIR positively regulated ELAVL1 expression by targeting miR-326, and downregulation of HOTAIR or ELAVL1 notably suppressed promotive effects of miR-326 inhibitor on MPP⁺ induced pyroptosis via activation of NLRP3 inflammasome. Collectively, HOTAIR silencing significantly inhibits neuronal damage through repressing NLRP3 mediated pyroptosis activation via regulation of miR-326/ELAVL1 axis in PD, which may contribute to a better understanding of PD pathogenesis and provide new treatment strategies for this disease.

帕金森病（PD）严重威胁人类健康。研究表明，长链非编码 RNA (lncRNA) 与 PD 之间存在密切相关性。然而，lncRNA 同源框转录反义 RNA (HOTAIR) 在 PD 中的生物学功能仍然很大程度上未知。^{在这项研究中，我们通过使用 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) 和 1-methyl-4-phenylpyridinium (MPP +} )建立了体内和体外 PD 模型来评估HOTAIR 在细胞焦亡和神经元损伤中的作用。RNA 免疫沉淀 (RIP) 和双荧光素酶报告基因测定用于验证 miR-326 与 HOTAIR 或 ELAV 样 RNA 结合蛋白 1 (ELAVL1) 之间的相互作用。LncRNA HOTAIR 在 PD 小鼠和 MPP ⁺诱导 SH-SY5Y 细胞。此外，HOTAIR 的敲低显着减轻了体内 PD 的症状。^{在MPP +}存在下，HOTAIR的下调可明显促进细胞活力并抑制含有3的NLR家族pyrin结构域（NLRP3）介导的SH-SY5Y细胞的细胞焦亡。此外，lncRNA HOTAIR 通过靶向 miR-326 正向调节 ELAVL1 表达，而 HOTAIR 或 ELAVL1 的下调显着抑制了 miR-326 抑制剂对 MPP ^{+的促进作用}通过激活 NLRP3 炎性体诱导细胞焦亡。总的来说，HOTAIR 沉默通过调节 PD 中的 miR-326/ELAVL1 轴来抑制 NLRP3 介导的细胞焦亡激活，从而显着抑制神经元损伤，这可能有助于更好地了解 PD 发病机制并为该疾病提供新的治疗策略。