Department of Pharmacology, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China.
Neurosci Lett. 2011 Feb 1;489(1):62-7. doi: 10.1016/j.neulet.2010.11.068. Epub 2010 Dec 4.
Accumulating evidences suggest that the related autophagy-lysosomal mechanism plays a critical role in many neurodegenerative disorders. In this study, we examined postmortem Parkinson's disease (PD) substantia nigra for evidence of cathepsin L by immunofluorescent staining, and found increased expression of cathepsin L in dopamine neurons of PD patients. We confirmed 6-OHDA induced nuclear translocation of cathepsin L in rat substantia nigral neurons as well. Furthermore, we observed autophagic vacuoles and lysosomes were accumulated in the 6-hydroxydopamine (6-OHDA) injured rat substantia nigra neurons with electron microscopy. Immunofluorescent staining showed that LC3 was enriched in dopamine neurons after 6-OHDA treatment. When pretreated with 3-methyladenine (3-MA), dopaminergic neurons were protected from cell death induced by 6-OHDA, associated with the suppression of LC3 and cathepsin L. Our results demonstrate that activation of autophagy and abnormal distribution of cathepsin L may be responsible for dopamine neuron death, involved in the pathogenic cascade event for the development of Parkinson's disease.
越来越多的证据表明，相关的自噬溶酶体机制在许多神经退行性疾病中起着关键作用。在这项研究中，我们通过免疫荧光染色检查了帕金森病（PD）患者死后的黑质，以寻找组织蛋白酶 L 的证据，并发现 PD 患者的多巴胺神经元中组织蛋白酶 L 的表达增加。我们还证实了 6-OHDA 诱导的大鼠黑质神经元中组织蛋白酶 L 的核易位。此外，我们通过电子显微镜观察到自噬小体和溶酶体在 6-羟多巴胺（6-OHDA）损伤的大鼠黑质神经元中积累。免疫荧光染色显示，6-OHDA 处理后 LC3 在多巴胺神经元中富集。用 3-甲基腺嘌呤（3-MA）预处理时，多巴胺能神经元可免受 6-OHDA 诱导的细胞死亡，这与 LC3 和组织蛋白酶 L 的抑制有关。我们的结果表明，自噬的激活和组织蛋白酶 L 的异常分布可能是多巴胺神经元死亡的原因，参与了帕金森病发展的致病级联事件。
