The study was conducted to assess the role of eukaryotic initiation factor 2 (eIF2α) in progressive dopaminergic neuronal death employing various interventions (YM08, 4μ8C, AEBSF, salubrinal, ursolic acid) of endoplasmic reticulum (ER) stress signaling. The protein level of all the ER stress related signaling factors (GRP78, IRE1α, ATF6, eIF2α, ATF4, XBP-1, GADD153) were estimated after 3 and 7 day of experiment initiation. Findings with single administration of interventions showed that salubrinal exhibited significant protection against rotenone induced adverse alterations in comparison to other interventions. Therefore, further study was expanded with repeat dose of salubrinal. Rotenone administration in rat brain caused the significant biochemical alterations, dose dependent progressive neuronal apoptosis and altered neuronal morphology which was significantly attenuated with salubrinal treatment. In conclusion, findings showed that rotenone administration caused the dose dependent progressive neuronal death including cardinal role of eIF2α, suggesting the potential pharmacological utilization of salubrinal or salubrinal like molecules in therapeutics of Parkinson's diseases.

该研究旨在评估真核起始因子 2 (eIF2α) 在进行性多巴胺能神经元死亡中的作用，采用内质网 (ER) 应激信号传导的各种干预措施（YM08、4μ8C、AEBSF、salubrinal、熊果酸）。实验开始后第 3 天和第 7 天评估所有 ER 应激相关信号因子（GRP78、IRE1α、ATF6、eIF2α、ATF4、XBP-1、GADD153）的蛋白质水平。单次干预措施的结果表明，与其他干预措施相比，salubrinal 对鱼藤酮引起的不良变化具有显着的保护作用。因此，通过重复剂量的 salubrinal 扩大了进一步的研究。大鼠大脑中的鱼藤酮给药引起了显着的生化变化，剂量依赖性进行性神经元凋亡和神经元形态改变，这种情况在 salubrinal 治疗后显着减弱。总之，研究结果表明，鱼藤酮给药引起剂量依赖性进行性神经元死亡，包括 eIF2α 的主要作用，这表明 salubrinal 或 salubrinal 样分子在帕金森病治疗中的潜在药理学用途。