Multhaup Gerhard, Huber Otmar, Buée Luc, Galas Marie-Christine
From the Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada,
the Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University, D-07743 Jena, Germany, and.
J Biol Chem. 2015 Sep 25;290(39):23515-22. doi: 10.1074/jbc.R115.677211. Epub 2015 Aug 21.
Amyloid precursor protein (APP) metabolites (amyloid-β (Aβ) peptides) and Tau are the main components of senile plaques and neurofibrillary tangles, the two histopathological hallmarks of Alzheimer disease. Consequently, intense research has focused upon deciphering their physiological roles to understand their altered state in Alzheimer disease pathophysiology. Recently, the impact of APP metabolites (APP intracellular fragment (AICD) and Aβ) and Tau on the nucleus has emerged as an important, new topic. Here we discuss (i) how AICD, Aβ, and Tau reach the nucleus and how AICD and Aβ control protein expression at the transcriptional level, (ii) post-translational modifications of AICD, Aβ, and Tau, and (iii) what these three molecules have in common.
淀粉样前体蛋白(APP)代谢产物(淀粉样β(Aβ)肽)和Tau蛋白是老年斑和神经原纤维缠结的主要成分,这两者是阿尔茨海默病的两个组织病理学标志。因此,大量研究集中在解读它们的生理作用,以了解它们在阿尔茨海默病病理生理学中的改变状态。最近,APP代谢产物(APP细胞内片段(AICD)和Aβ)和Tau蛋白对细胞核的影响已成为一个重要的新课题。在此,我们讨论:(i)AICD、Aβ和Tau蛋白如何进入细胞核以及AICD和Aβ如何在转录水平上控制蛋白质表达;(ii)AICD、Aβ和Tau蛋白的翻译后修饰;以及(iii)这三种分子的共同之处。