Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding.
Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding.
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DOI：
10.1186/1471-2202-8-29
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发表时间：
2007-05-02
期刊：
影响因子：
2.4
通讯作者：
Chakrabartty, Avijit
中科院分区：
文献类型：
--
作者：
Bateman, David A.;McLaurin, JoAnne;Chakrabartty, Avijit
已知淀粉样肽Aβ40和Aβ42的聚集参与阿尔茨海默病（AD）的病理学。在这里，我们研究了三种形式的Aβ（Aβ40，Aβ42和Aβ突变体）的肽聚集和细胞表面结合之间的关系。使用共聚焦显微镜和流式细胞术与荧光标记的Aβ，我们证明了阿尔茨海默氏症淀粉样肽的聚集倾向和它们的神经元细胞表面缔合之间的相关性。我们发现高聚集倾向的Aβ42在1小时内与神经元细胞表面结合，而低聚集倾向的Aβ40在24小时内与神经元细胞表面结合。我们发现，Aβ42的双重突变降低了其聚集倾向，也降低了其与细胞表面的关联。此外，我们发现对Aβ细胞毒性具有抗性的细胞系，非神经元人类淋巴瘤细胞系U937，不结合Aβ40或Aβ42。总之，我们的研究结果表明，淀粉样肽聚集倾向是神经细胞表面协会的一个重要决定因素。我们预计，我们的方法，涉及在活细胞中的Aβ成像，将是非常有用的治疗药物，防止毒性Aβ与神经元细胞的关联的疗效进行评估。
Aggregation of the amyloid peptides, Aβ40 and Aβ42, is known to be involved in the pathology of Alzheimer's disease (AD). Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Aβ (Aβ40, Aβ42, and an Aβ mutant). Using confocal microscopy and flow cytometry with fluorescently labelled Aβ, we demonstrate a correlation between the aggregation propensity of the Alzheimer amyloid peptides and their neuronal cell surface association. We find that the highly aggregation prone Aβ42 associates with the surface of neuronal cells within one hour, while the less aggregation prone Aβ40 associates over 24 hours. We show that a double mutation in Aβ42 that reduces its aggregation propensity also reduces its association with the cell surface. Furthermore, we find that a cell line that is resistant to Aβ cytotoxicity, the non-neuronal human lymphoma cell line U937, does not bind either Aβ40 or Aβ42. Taken together, our findings reveal that amyloid peptide aggregation propensity is an essential determinant of neuronal cell surface association. We anticipate that our approach, involving Aβ imaging in live cells, will be highly useful for evaluating the efficacy of therapeutic drugs that prevent toxic Aβ association with neuronal cells.
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DOI：
10.1073/pnas.89.6.2252
发表时间：
1992-03-15
影响因子：
11.1
作者：
CAPORASO, GL;GANDY, SE;GREENGARD, P
通讯作者：
GREENGARD, P
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
2.9
作者：
Burdick, D;Kosmoski, J;Glabe, CG
通讯作者：
Glabe, CG
影响因子：
5.6
作者：
Gorman, PM;Yip, CM;Chakrabartty, A
通讯作者：
Chakrabartty, A
影响因子：
5.3
作者：
Hayashi, H;Kimura, N;Yanagisawa, K
通讯作者：
Yanagisawa, K