Lee Yung-Shih, Feng Chien-Wei, Peng Mei-Yu, Chan Te-Fu, Chen Yu-Chieh
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan.
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807377, Taiwan.
Parkinsons Dis. 2021 Oct 22;2021:3064892. doi: 10.1155/2021/3064892. eCollection 2021.
Few pharmaceutical agents for slowing Parkinson's disease (PD) progression existed, especially for perimenopause females. The current general medications are mostly hormone replacement therapy and may have some side effects. Therefore, there is an urgent need for a novel treatment for PD. This study examined the possibility of estradiol plus lithium chloride (LiCl), one of the metal halides used as an alternative to salt. We showed that the combination of LiCl and estradiol could enhance neurogenesis proteins GAP-43 and N-myc in the human neuronal-like cells. We also further confirmed the neurogenesis activity in zebrafish. LiCl and LiCl plus estradiol could enhance 6-OHDA-induced upregulation of TGase-2b and Rho A mRNA expression. Besides, LiCl plus estradiol showed a synergic effect in anti-apoptotic activity. LiCl plus estradiol protected SH-SY5Y cells and zebrafish against 6-OHDA-induced damage on neurons than LiCl or estradiol alone groups via p-P38, p-Akt, Bcl-2, and caspase-3 cascade. The potential for developing this combination as a candidate treatment for PD is discussed.
用于减缓帕金森病（PD）进展的药物制剂很少，尤其是对于围绝经期女性。目前常用的药物大多是激素替代疗法，且可能有一些副作用。因此，迫切需要一种治疗PD的新方法。本研究探讨了雌二醇加氯化锂（LiCl）的可能性，LiCl是一种用作盐替代品的金属卤化物。我们发现LiCl和雌二醇的组合可以增强人神经元样细胞中神经发生蛋白GAP-43和N-myc的表达。我们还进一步证实了斑马鱼中的神经发生活性。LiCl和LiCl加雌二醇可以增强6-OHDA诱导的TGase-2b和Rho A mRNA表达上调。此外，LiCl加雌二醇在抗凋亡活性方面表现出协同作用。与单独使用LiCl或雌二醇的组相比，LiCl加雌二醇通过p-P38、p-Akt、Bcl-2和caspase-3级联反应保护SH-SY5Y细胞和斑马鱼免受6-OHDA诱导的神经元损伤。本文讨论了将这种组合开发为PD候选治疗方法的潜力。
