Understanding the molecular basis of Alzheimer's disease using a Caenorhabditis elegans model system.
Understanding the molecular basis of Alzheimer's disease using a Caenorhabditis elegans model system.
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DOI：
10.1007/s00429-009-0235-3
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发表时间：
2010-03
影响因子：
3.1
通讯作者：
Li, Chris
中科院分区：
文献类型：
--
作者：
Ewald, Collin Y.;Li, Chris
阿尔茨海默病（AD）是美国痴呆症的主要原因。在细胞水平，AD患者的脑的特征在于细胞外致密斑块和细胞内神经元缠结，其主要组分分别是β-淀粉样肽和tau。β-淀粉样肽是淀粉样前体蛋白（APP）的裂解产物; APP中的突变与少数家族性阿尔茨海默病病例相关。APP是APP家族的典型成员，其功能尚不清楚。线虫秀丽隐杆线虫是最重要的遗传工具之一，正以各种方式用于研究APP的功能，并确定β-淀粉样肽和tau蛋白如何诱导毒性。第一，C. elegans APP相关基因apl-1正在研究中。尽管不同的生物体可能在不同的功能环境中使用APP和相关蛋白质，如APL-1，但它们发挥功能的途径和与它们相互作用的分子通常是保守的。其次，通过对C.优雅的第三，为了解决毒性、变性发作和保护机制的问题，将不同的人β-淀粉样肽和tau变体引入C。elegans和所得的转基因系进行了检测。在这里，我们总结了一个简单的系统，如C。秀丽线虫可以作为一个模型来了解APP功能和抑制β-淀粉样肽和tau毒性在高等生物体。
Alzheimer’s disease (AD) is the major cause of dementia in the United States. At the cellular level, the brains of AD patients are characterized by extracellular dense plaques and intracellular neurofibrillary tangles whose major components are the β-amyloid peptide and tau, respectively. The β-amyloid peptide is a cleavage product of the amyloid precursor protein (APP); mutations in APP have been correlated with a small number of cases of familial Alzheimer’s disease. APP is the canonical member of the APP family, whose functions remain unclear. The nematode Caenorhabditis elegans, one of the premier genetic workhorses, is being used in a variety of ways to address the functions of APP and determine how the β-amyloid peptide and tau can induce toxicity. First, the function of the C. elegans APP-related gene, apl-1, is being examined. Although different organisms may use APP and related proteins, such as APL-1, in different functional contexts, the pathways in which they function and the molecules with which they interact are usually conserved. Second, components of the γ-secretase complex and their respective functions are being revealed through genetic analyses in C. elegans. Third, to address questions of toxicity, onset of degeneration, and protective mechanisms, different human β-amyloid peptide and tau variants are being introduced into C. elegans and the resultant transgenic lines examined. Here, we summarize how a simple system such as C. elegans can be used as a model to understand APP function and suppression of β-amyloid peptide and tau toxicity in higher organisms.
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影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
DOI：
10.1111/j.1749-6632.1955.tb42463.x
发表时间：
1955-01-01
期刊：
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES
影响因子：
--
作者：
BLEULER, M;STOLL, WA
通讯作者：
STOLL, WA
影响因子：
2.7
作者：
Cinar, HN;Sweet, KL;Newman, AP
通讯作者：
Newman, AP
影响因子：
4.4
作者：
DELACOURTE, A;DEFOSSEZ, A
通讯作者：
DEFOSSEZ, A
影响因子：
4.8
作者：
Ermekova, KS;Zambrano, N;Sudol, M
通讯作者：
Sudol, M