From Soluble Aβ to Progressive Aβ Aggregation: Could Prion-Like Templated Misfolding Play a Role?
From Soluble Aβ to Progressive Aβ Aggregation: Could Prion-Like Templated Misfolding Play a Role?
复制标题
DOI：
10.1111/bpa.12049
复制
发表时间：
2013-05-01
期刊：
影响因子：
6.4
通讯作者：
Eisele, Yvonne S.
中科院分区：
文献类型：
--
作者：
Eisele, Yvonne S.
A肽的积累、聚集和沉积是阿尔茨海默病（AD）或脑淀粉样血管病（A- caa）患者大脑中的病理标志。虽然A是一种功能未知的肽，但它在人脑中不断产生，通常处于可溶性状态。然而，A肽具有聚集倾向，因为它们具有内在的能力，可以采用富含片状结构的替代构象，聚集成低聚体和纤维状结构。这种从可溶性到聚集态的转变被假设为引发病理级联反应，因此需要深入研究。越来越多的证据表明，朊病毒样模板错误折叠是促进进行性A聚集的生化现象。在这里，我们回顾了体外和体内的研究，这些研究表明大脑A聚集确实可能通过朊病毒样模板错误折叠进行。本文讨论了这些发现的意义，以了解疾病的发生和进展以及开发治疗方法。
Accumulation, aggregation and deposition of A peptides are pathological hallmarks in the brains of individuals affected by Alzheimer's disease (AD) or by cerebral -amyloid angiopathy (A-CAA). While A is a peptide of yet largely unknown function, it is constantly produced in the human brain where it normally remains in a soluble state. However, A peptides are aggregation prone by their intrinsic ability to adopt alternative conformations rich in -sheet structure that aggregate into oligomeric as well as fibrillar formations. This transition from soluble to aggregated state has been hypothesized to initiate the pathological cascade and is therefore subject to intensive research. Mounting evidence suggests prion-like templated misfolding as the biochemical phenomenon responsible for promoting progressive A aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral A aggregation may indeed progress via prion-like templated misfolding. The implications of these findings are discussed with respect to understanding initiation and progression of the disease and to developing therapeutics.