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    Please use this identifier to cite or link to this item: http://nccur.lib.nccu.edu.tw/handle/140.119/115363


    Title: 神經恢復性藥物治療帕金森氏症之研發
    Authors: 詹銘煥
    Contributors: 神經科學研究所
    Keywords: 新木脂素;神經滋養因子;神經纖維增長;多巴胺;帕金森氏症
    neolignan;neurotrophic factor;neurite outgrowth;dopamine;Parkinson’s disease
    Date: 2014
    Issue Date: 2017-12-25 14:51:28 (UTC+8)
    Abstract: 研究團隊的近期論文闡釋體外實驗中新合成新木脂素包含MH101及其衍生物可拮抗神經毒素引起神經細胞死亡,顯示他們具有神經保護功能。本研究使用新合成新木脂素(MH101-MH107)進一步探討這些新木脂素對於神經細胞的保護與滋養作用。透過腎上腺髓質嗜鉻細胞瘤 PC12 細胞預先處理新合成新木脂素,並以過氧化氫(H2O2)使細胞產生氧化壓力,之後利用活性氧檢測試驗(DCFH-DA assay)偵測細胞內活性氧(reactive oxygen species, ROS)的含量。實驗結果顯示,預先處理較高濃度(3-10μM)的新合成新木脂素顯著降低過氧化氫所產生的氧化壓力。另以H2O2誘導PC12細胞死亡,並使用MTT試驗法,觀測新木脂素對於細胞存活的影響。結果顯示新木脂素顯著減少H2O2造成的細胞死亡,此結果與其抗氧化壓力有一致性結果。於神經滋養實驗,發現這些新木脂素本身無法直接誘導PC12細胞的神經突生長。因此,使用神經滋養因子(nerve growth factor, NGF)誘導PC12細胞神經突生長,發現新木脂素在低濃度(0.1-1μM)顯著加強神經突生長。另一方面在體內動物實驗中,實驗結果表示新木脂素中MH101及MH102不僅可預防並且修補恢復因神經毒素6-OHDA引起的小鼠運動功能失調及多巴胺神經毒害。因此,據此推測新木脂素MH101及其新型類似物可能經由神經滋養特性以解救神經退化性疾病的神經傷害與肢體運動功能缺陷。然而,有關新木脂素(neolignan)的分子標的及藥理機轉仍然混沌不清,仍需要進一步的研究。
    Our previous report indicated that the new synthesized neolignans including MH101 and its novel derivatives exhibited the neuroprotective activity against neurotoxin-induced neuronal cell death in vitro. Thus, we predicted that these novel neolignans may conduct the trophic and protective effects on neurons. Using the PC12 cell model, it was observed that neolignans (MH101-107) at higher concentrations of 3-10 μM reduced the increases in reactive oxygen species (ROS) level and cell damage induced by hydrogen peroxide (H2O2) exposure. Neolignans at higher concentration (10-30 μM) also decreased the cell death by H2O2 exposure for 24 hours. As to the neurotrophic effects, neolignans alone did not induce neurite outgrowth. However, these neolignans significantly potentiated nerve growth factor (NGF) induced neurite outgrowth in a concentration-dependent manner (0.1-1 μM). In vivo studies, current data further demonstrated that the selective neolignans MH101 and MH102 could both prevent and restore the dopaminergic (DA) neuron damage and motor dysfunctions elicited by 6-hydroxydopamine (6-OHDA) in mice. Thus, it is likely that neolignan MH101 and its novel derivatives might exert their neuronal restorative actions and neurotrophic activity to rescue neuronal impairment and motor dysfunction in neurodegenerative diseases. However, the molecular targets and pharmacological mechanism of neolignans are still unclear and required further studies.
    Relation: 執行起迄:2014/08/01~2015/07/31
    103-2320-B-004-002
    Data Type: report
    Appears in Collections:[神經科學研究所 ] 國科會研究計畫

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