中文摘要：

α-突触核蛋白（α-synuclein，α-SN）和泛素-蛋白酶体系统（ubiquitin—proteasome system，ups）在帕金森病发病过程中都起着重要作用，探讨两者在多巴胺能神经细胞死亡过程中的相互关系有重要意义。本文分别采用不同浓度的重组人α-SN、蛋白酶体活性抑制剂lactacystin单独处理，或与多巴胺能神经细胞特异毒素6-羟基多巴胺（6-OHDA）联合处理多巴胺能神经细胞系SH—SY5Y细胞，然后检测细胞活性和蛋白酶体活性。结果显示，α-SN依据浓度的不同而具有神经保护或神经毒性的双重作用。5p．mol／L以下浓度的α-SN可对抗6-OHDA对SH—SY5Y细胞的毒性，并有一定促增殖作用；10μmol／L以上浓度cα-对细胞有毒性作用，并加重了6-OHDA的细胞毒性。采用相应浓度的lactacystin处理，获得与α-SN处理相似的结果，而MEK1／2特异抑制剂PD98059T预则可完全阻断低浓度α-SN和lactacystin的神经保护作用。以上结果提示，不同浓度α-SN对SH—SY5Y细胞的6-OHDA神经毒性的双重作用是通过抑制蛋白酶体活性实现的，而其对神经细胞的保护作用和MAPK途径相关。

英文摘要：

α-synuclein （α-SN） has been postulated to play a pivotal role in the pathogenesis of Parkinson＇s disease （PD）. However, the physiological functions of α-SN and the molecular and cellular mechanisms underlying neuronal loss remain unclear. Recent studies suggest that α-SN plays dual roles of neuroprotection and neurotoxicity depending on its concentration or level of expression. In the present study, we explored the potential mechanisms for α -SN to regulate neuronal survival, α-SN at different concentrations （0.1 to 40 μmol/L） with or without 50 μmol/L 6-hydroxydopamine （6-OHDA） were added into the culture medium of the SH-SY5Y dopaminergic neural cells. The cell viability was measured on post-treatment day 1, 2 and 3. The activity of proteasome inhibited by α-SN was tested by a proteasome activity assay system after 2 h of α-SN treatment. According to the activity of proteasome inhibited by α-SN, the correlative dose of proteasome inhibitor-lactacystin （10 nmol/L to 5 μmol/L） with or without 50 μmol/L 6-OHDA were used and the cell viability was assayed on post-treatment day 1, 2 and 3. The results showed that α-SN played dual roles ofneuroprotection and neurotoxicity depending on its concentration. At low concentration （0.1 to 5 μmol/L）, α-SN promoted the proliferation and protected neurons against the neurotoxicity of 6-OHDA; in contrast, at high concentration （10 to 40 μmol/L）, α-SN possessed cytotoxicity. The results of lactacystin treatment implied that the dual roles of α-SN were related to the moderate and strong inhibition of proteasome activity. The MEK1/2 specific inhibitor PD98059 completely blocked the protection of both α-SN and lactacystin, suggesting that MAPK pathway might be involved in the neuroprotection of α-SN.