中草藥純物質TR及AG透過麩胺酸接受器減緩Aβ誘導之神經病變

Pure compounds TR and AG within Chinese herbal medicines mediate glutamate receptors to attenuate Aβ-induced neuronal pathophysiology.

郭力禎(Kuo Li-Chen)

指導教授 ： 林炎壽

國立臺灣師範大學/理學院/生命科學系/碩士(2016年)

https://doi.org/10.6345/NTNU202204497

摘要

['阿茲海默症(Alzheimer’s disease, AD)是常見的神經退化性疾病，導致病患逐漸喪失記憶並產生認知功能的障礙，本研究探討可以減緩Aβ誘導神經病變的中草藥及其機轉。研究指出Aβ 寡聚體會過度活化麩胺酸接受器，包括AMPA receptor、NMDA receptor、Kainate receptor及mGluR1/5，進而造成神經細胞不正常去極化、導致細胞死亡。利用DiBAC4(3)膜電位螢光染劑做為藥物篩選平台，可以觀察到Aβ寡聚體誘導神經細胞不正常去極化的現象，於之前利用此平台篩選所得的幾種有效中草藥物中，目前針對其中兩種純物質進行進一步研究，暫時分別命名為TR及AG，發現TR及AG會調節NMDA接受器或AMPA接受器來減緩神經不正常去極化。在藥理機轉方面，我們推測AG可能參與未在本研究探討的訊息傳遞分子範圍，因此尚未找到其有效機轉，然而AG具有類似NMDA接受器拮抗劑及AMPA接受器拮抗劑的特性，提供未來臨床阿茲海默症患者一個具潛力性的治療及解決方案。']

關鍵字

阿茲海默症 ； β類澱粉蛋白 ； 麩胺酸接受器 ； 中草藥 ； DiBAC4(3)

並列摘要

['Alzheimer’s disease (AD), a progressive neurodegenerative disease leads to memory impairment and other cognitive problems. Recent studies have indicated that the synaptic dysfunction induced by Aβ oligomer is dependent on overstimulation of glutamate receptors such as N-methyl-D-aspartate receptors (NMDARs), AMPA receptors (AMPARs), kainite receptors, and mGluR1/5. Utilizing DiBAC4(3), a slow response voltage-sensitive fluorescent dye, we have established a drug screening platform. After screening for ~12 herbal medicines, we focus on two pure compounds, named TR and AG, which are able to ameliorate Aβ-induced depolarization. We found that these two pure compounds mediate NMDA receptors and AMPA receptors to execute such effects. Currently, we have not revealed more molecular/signaling mechanism regarding of AG. Overall, the finding that AG can be used as NMDA receptor antagonist and AMPA receptor antagonist offers a great potential for developing a new therapeutic drug for treatment of AD patients.']

並列關鍵字

Alzheimer’s disease ； amyloid beta ； DiBAC4(3) ； glutamate receptor ； Chinese herbal medicines

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