黨參之有效化合物(C-9)降低由Protein-X誘發之類澱粉蛋白細胞毒性及蛋白寡聚合之機轉探討

An active compound (C-9) of Chinese herbal medicine, Codonopsis pilosula, decreased the oligomerization of amyloid-beta and cytotoxicity of SH-SY5Y cells induced by a novel biomarker-Protein-X.

林晨揚(Lin Chen-Yang)

指導教授 ： 林榮耀

國立臺灣師範大學/理學院/生命科學系/碩士(2017年)

https://doi.org/10.6345/NTNU202201924

摘要

["阿茲海默氏症(Alzheimer's disease, AD)是最常見的神經退化性疾病之一，好發於65歲以上的老年人口，阿茲海默氏症主要是由β-類澱粉蛋白(amyloid beta, Aβ)堆積形成類澱粉斑塊(amyloid plaques)和過度磷酸化Tau蛋白(p-tau)造成的神經纖維糾結導致神經細胞的損傷。先前研究顯示，Aβ會聚集形成不同的型態(forms)，其中寡聚類澱粉蛋白(Aβ oligomer)具有較高的毒性。所以發展具有抑制Aβ聚集(aggregation)的藥物是治療阿茲海默氏症的策略之一。在我們先前的實驗中發現，兩年大的阿茲海默氏症模式鼠中，具有較高表現的Protein-X。為了確認Protein-X在阿茲海默氏症中的機制，我們建立了Protein-X stable transfected SH-SY5Y的細胞株。發現Protein-X表現的情況下，細胞產生較高的細胞毒性之寡聚合Aβ聚集(Aβ oligomerization)。我們也在黨參中發現化合物9(C-9)，可以降低細胞毒性及寡聚合Aβ的聚集。故是發展治療阿茲海默氏症藥物的潛力藥物。"]

關鍵字

阿茲海默氏症 ； 中草藥 ； 類澱粉蛋白 ； X蛋白

並列摘要

['Alzheimer’s disease (AD), the most common neurodegenerative disease, usually occurs in people over 65 years of age. AD is well known caused by the accumulation of misfolded amyloid beta (Aβ) plaques and hyperphosphorylated tau protein-containing neurofibrillary tangles, leading to neuronal cell death. Many studies showed that Aβ oligomer has higher toxicity than that of Aβ monomers, and the development of potential drug which can reduce or inhibit the formation of Aβ oligomer would possibly prevent AD. Previously, we found that Protein-X is highly expressed in 2 years old triple transgenic AD mice [PS1(M146V), APP(K670M/N671L), tau(P301L)]. To confirm the effects of Protein-X in AD pathway, we recently generated Protein-X stable transfected SH-SY5Y cell line, and found that SH-SY5Y cells are more sensitive to Aβ treatment and have higher Aβ oligomerization in the presence of Protein-X. We also identified that compound-9 (C-9) which is isolated for Codonopsis pilosula (CP) can reduce Aβ formation and cytotoxicity in Protein-X stable transfected Sh-SY5Y cells. Based on the these results, C-9 could be a potential therapeutic drug for the treatment of AD.']

並列關鍵字

Alzheimer’s disease ； Chinese herbal medicine ； amyloid beta ； Protein-X

參考文獻

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