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J Cell Sci:利用单细胞生物研究AD相关蛋白的功能

  1. AD
  2. 单细胞生物

来源:生物谷 2014-01-24 22:30

2014年1月24日讯 /生物谷BIOON/--近日,科学家成功使用简单的单细胞变形虫(阿米巴)来了解人类蛋白质--早老素(Presenilin)蛋白在阿尔茨海默氏症中的功能。

新研究发表在Journal of Cell Science杂志上,揭示了阿米巴如何将能更好地用于理解这些阿尔茨海默氏症疾病相关蛋白细胞中的功能,而无需在动物身上开展测试。此研究的最终目的是开发治疗退行性疾病的新途径。

早老素(Presenilin)蛋白突变导致遗传性形式的阿尔茨海默病,这些蛋白质在年龄相关疾病中也发挥了重要作用。然而,了解这些蛋白质的作用是困难的,因为缺乏蛋白质的细胞是不能存活的。

早老素蛋白已被广泛研究分析,在此研究领域常用动物开展研究,但这些实验是有问题的,因为动物细胞中缺失蛋白质后会导致存活率降低并阻止发育。而这一新发现使得能够在细胞中研究人早老素蛋白的作用,而不使用动物进行测试。(生物谷Bioon.com)

 

An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum

Marthe H. R. Ludtmann, Grant P. Otto, Christina Schilde, Zhi-Hui Chen, Claire Y. Allan, Selina Brace, Philip W. Beesley, Alan R. Kimmel, Paul Fisher, Richard Killick and Robin S. B. Williams

Mutations in two presenilin genes cause familial Alzheimer's disease. Presenilins have both proteolysis-dependent functions as components of the γ-secretase complex and proteolysis-independent functions in signalling. In this study we investigate a conserved function of human presenilins in the development of the simple model Dictyostelium discoideum. We show that the block in Dictyostelium development caused by ablation of both Dictyostelium presenilins is rescued by expression of human presenilin 1, restoring terminal differentiation of multiple cell types. This developmental role is independent of proteolytic activity, since mutation of both catalytic aspartates does not affect presenilin ability to rescue development, and ablation of nicastrin, a γ-secretase component critical for proteolytic activity, does not block development. The role of presenilins during Dictyostelium development is therefore independent of their proteolytic activity. However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP) levels and enhanced stimulation-induced calcium release, suggesting that presenilins regulate these intracellular signalling pathways. Our data suggest that presenilin proteins perform an ancient non-proteolytic role in regulating intracellular signalling and development, and that Dictyostelium is a useful model for analysing human presenilin function.

 

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