Macromolecular and small-molecule modulation of intracellular A beta(42) aggregation and associated toxicity
文献类型：期刊论文
| 作者 | Chakrabortee, Sohini1; Liu, Yun4; Zhang, Liao4; Matthews, Helena R.1; Zhang, Hanrui3; Pan, Ni3; Cheng, Chun-ru2; Guan, Shu-hong2 ; Guo, De-an2; Huang, Zebo3
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| 刊名 | BIOCHEMICAL JOURNAL
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| 出版日期 | 2012-03-15 |
| 卷号 | 442页码:507-515 |
| 关键词 | amyloid beta-peptide (A,beta) late embryogenesis abundant (LEA) protein protein aggregation polysaccharide traditional Chinese medicine |
| ISSN号 | 0264-6021 |
| DOI | 10.1042/BJ20111661 |
| 文献子类 | Article |
| 英文摘要 | A beta (amyloid beta-peptide) has a central role in AD (Alzheimer's disease) where neuronal toxicity is linked to its extracellular and intracellular accumulation as oligomeric species. Searching for molecules that attenuate A beta aggregation could uncover novel therapies for AD, but most studies in mammalian cells have inferred aggregation indirectly by assessing levels of secreted A beta peptide. In the present study we establish a mammalian cell system for the direct visualization of At formation by expression of an A beta(42)-EGFP (enhanced green fluorescent protein) fusion protein in the human embryonic kidney cell line T-REx293, and use this to identify both macromolecules and small molecules that reduce aggregation and associated cell toxicity. Thus a molecular shield protein AavLEA1 [Aphelencluis avenue LEA (late embryogenesis abundant) protein 1] which limits aggregation of proteins with expanded poly(Q) repeats, is also effective against A beta(42)-EGFP when co-expressed in T-REx293 cells. A screen of polysatcharide and small organic molecules from medicinal plants and fungi reveals one candidate in each category, PS5 (polysaccharide 5) and ganoderic acid DM respectively, with activity against A beta. Both PS5 and ganoderic acid DM probably promote A beta aggregate clearance indirectly through the proteasome. The model is therefore of value to study the effects of intracellular At on cell physiology and to identify reagents that counteract those effects. |
| WOS关键词 | BETA-AMYLOID PEPTIDE ; FUNGUS GANODERMA-LUCIDUM ; ALPHA-B-CRYSTALLIN ; ALZHEIMERS-DISEASE ; DESICCATION TOLERANCE ; NATURAL-PRODUCTS ; IN-VITRO ; ACID-DM ; PROTEIN ; ACCUMULATION |
| 资助项目 | European Research Council[233232] ; Biotechnology and Biological Sciences Research Council[1603] ; Royal Society[00000000] ; Broodbank Trust[00000000] ; Hughes Hall, Cambridge[00000000] ; Chinese Academy of Sciences[KSCX2-YW-R-166] ; National Natural Science Foundation of China[30973664] ; National Natural Science Foundation of China[30811130217] ; National Natural Science Foundation of China[31070230] ; Shenzhen City, China[CXB201005240008A] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000301559600005 |
| 出版者 | PORTLAND PRESS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278154]  |
| 专题 | 成果转移转化处 上海中药现代化研究中心 |
| 通讯作者 | Tunnacliffe, Alan |
| 作者单位 | 1.Univ Cambridge, Dept Chem Engn & Biotechnol, Cell & Organism Engn Lab, Cambridge CB2 3RA, England; 2.Chinese Acad Sci, Natl Engn Lab TCM Standardizat Technol, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China 3.Wuhan Univ, Sch Pharmaceut Sci, Key Lab Combinatorial Biosynth & Drug Discovery, Wuhan 430071, Peoples R China; 4.Shenzhen Univ, Sch Life Sci, Shenzhen 518060, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chakrabortee, Sohini,Liu, Yun,Zhang, Liao,et al. Macromolecular and small-molecule modulation of intracellular A beta(42) aggregation and associated toxicity[J]. BIOCHEMICAL JOURNAL,2012,442:507-515. |
| APA | Chakrabortee, Sohini.,Liu, Yun.,Zhang, Liao.,Matthews, Helena R..,Zhang, Hanrui.,...&Tunnacliffe, Alan.(2012).Macromolecular and small-molecule modulation of intracellular A beta(42) aggregation and associated toxicity.BIOCHEMICAL JOURNAL,442,507-515. |
| MLA | Chakrabortee, Sohini,et al."Macromolecular and small-molecule modulation of intracellular A beta(42) aggregation and associated toxicity".BIOCHEMICAL JOURNAL 442(2012):507-515. |
入库方式： OAI收割
来源：上海药物研究所
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