本文關(guān)鍵詞： 阿爾茨海默癥 Aβ 共組裝 自噬降解 協(xié)同　出處：《東北師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：阿爾茨海默癥,是一種最典型的神經(jīng)性退行性疾病。近年來,關(guān)于阿爾茨海默癥治療研究所面臨的一個最大挑戰(zhàn)是如何保持體內(nèi)β淀粉樣蛋白(Aβ)的平衡。納米材料,由于其獨(dú)有的特性,在眾多疾病治療領(lǐng)域中被廣泛使用,包括常見的神經(jīng)性疾病領(lǐng)域,具有重大的生物應(yīng)用價值。其中,多肽-聚合物納米材料作為一種新型的功能化材料,具有良好的生物相容性和安全性。將此聚合物材料有針對性地修飾上具有不同生物效應(yīng)的多肽殘基之后,可以有效地實(shí)現(xiàn)單一材料具備多種生物效應(yīng),從而提高藥物療效。所制備的納米材料不僅可以提高抗阿爾茨海默癥活性,也對阿爾茨海默癥的治療效果作出有效的評估,具有重要的研究意義和潛在的藥物應(yīng)用價值。我們首先合成了丙烯�；臍ぞ厶蔷酆衔�(Acryl-CS)和含有分子間多重氫鍵的多肽殘基CFFVLKG-PEG368,并分別通過核磁共振(NMR)和飛行質(zhì)譜對其進(jìn)行了表征。接著,我們將CFFVLKG-PEG368與自噬激活肽Beclin-1(CTNVFNATFHIWHSGQFGT)按照1:1的比例,通過邁克爾加成反應(yīng)方式與Acryl-CS進(jìn)行反應(yīng),進(jìn)而得到多肽-聚合物體系CS-K-B(M3),利用NMR對其結(jié)構(gòu)進(jìn)行了表征。該聚合物多肽M3在緩沖溶液中會自組裝成納米顆粒,通過透射電子顯微鏡(TEM)對其形貌進(jìn)行表征,顯示為直徑為43.8±11.1 nm納米顆粒。一方面,M3納米材料中含有Aβ的同源序列KLVFF,可以識別Aβ并與其共組裝,進(jìn)而阻止Aβ的纖維化;另一方面,由于M3功能化修飾了自噬激活肽Beclin-1,可以上調(diào)細(xì)胞的自噬,因此,當(dāng)M3與Aβ組成的共組裝體進(jìn)入細(xì)胞之后細(xì)胞的自噬功能被激活或上調(diào),進(jìn)而通過自噬降解Aβ。因此,兩種相互協(xié)同的策略,能夠?qū)崿F(xiàn)阿爾茨海默癥有效治療。
[Abstract]:Alzheimer's disease is one of the most typical neurodegenerative diseases. In recent years, one of the biggest challenges facing the Alzheimer disease treatment institute has been how to maintain the balance of beta-amyloid A 尾 in the body. Because of its unique characteristics, it has been widely used in many fields of disease treatment, including common neurological diseases, and has great biological application value. Among them, polypeptide polymer nanomaterials as a new type of functional materials, It has good biocompatibility and safety. By modifying the polypeptide residues with different biological effects, we can realize that the single material has many biological effects. To improve the efficacy of the drug. The prepared nanomaterials not only improve the anti-Alzheimer 's activity, but also effectively evaluate the efficacy of the treatment of Alzheimer's disease. It has important research significance and potential drug application value. Firstly, we synthesized acryl-CSA, a chitosan polymer, and polypeptide residues containing intermolecular multiple hydrogen bonds, CFFVLKG-PEG368, which were synthesized by NMR and FMS, respectively. It was characterized. Then, We reacted CFFVLKG-PEG368 with the autophagy activating peptide Beclin-1 CTNVFNATFHIWHSGQFGT1 at 1: 1 by Michael's addition reaction with Acryl-CS. The structure of CS-K-BN M3N was characterized by NMR. The polypeptide M3 was self-assembled into nanoparticles in buffer solution and characterized by transmission electron microscopy (TEM). On the one hand, the homologous sequence KLVFFFF containing A 尾 in the M3 nanomaterials can recognize A 尾 and co-assemble with it, thereby preventing the fibrosis of A 尾. Since M3 functionalizes the autophagy activating peptide Beclin-1, it can up-regulate the autophagy of the cells. Therefore, the autophagy function of the cells is activated or upregulated when the co-assembly of M3 and A 尾 enters the cell, and the autophagy degrades A 尾 through autophagy. Two synergistic strategies can be used to effectively treat Alzheimer's disease.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.1;TB383.1

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本文編號：1517964