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β-淀粉样蛋白合成的三十年:挑战与进展

Three Decades of Amyloid Beta Synthesis: Challenges and Advances.

作者信息

Kasim Johanes K, Kavianinia Iman, Harris Paul W R, Brimble Margaret A

机构信息

School of Biological Sciences, The University of Auckland, Auckland, New Zealand.

Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand.

出版信息

Front Chem. 2019 Jul 2;7:472. doi: 10.3389/fchem.2019.00472. eCollection 2019.

Abstract

Aggregation of the pathological amyloid beta (Aβ) isoform Aβ into senile plaques is a neuropathological hallmark of Alzheimer's disease (AD). The biochemical significance of this phenomenon therefore necessitates the need for ready access to Aβ for research purposes. Chemical synthesis of the peptide, however, is technically difficult to perform given its propensity to aggregate both on resin during solid phase peptide synthesis and in solution during characterization. This review presents a chronological summary of key publications in the field of Aβ synthesis, dating back from its maiden synthesis by Burdick et al. Challenges associated with the preparation of Aβ were identified, and the solutions designed over the course of time critically discussed herein. Ultimately, the intention of this review is to provide readers with an insight into the progress that has been made in the last three decades, and how this has advanced broader research in AD.

摘要

病理性淀粉样β(Aβ)亚型聚集成老年斑是阿尔茨海默病(AD)的神经病理学标志。因此,这一现象的生化意义使得有必要为研究目的而方便地获取Aβ。然而,鉴于该肽在固相肽合成过程中在树脂上以及在表征过程中在溶液中均易于聚集,其化学合成在技术上难以进行。本综述按时间顺序总结了Aβ合成领域的关键出版物,可追溯到Burdick等人首次合成Aβ之时。确定了与Aβ制备相关的挑战,并在此对长期以来设计的解决方案进行了批判性讨论。最终,本综述旨在让读者深入了解过去三十年所取得的进展,以及这如何推动了AD领域更广泛的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a03/6614915/09de9da54be2/fchem-07-00472-g0001.jpg

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