Critical role of intraneuronal Aβ in Alzheimer's disease: technical challenges in studying intracellular Aβ.
Critical role of intraneuronal Aβ in Alzheimer's disease: technical challenges in studying intracellular Aβ.
复制标题
DOI：
10.1016/j.lfs.2012.06.004
复制
发表时间：
2012-12-10
期刊：
影响因子：
6.1
通讯作者：
Tampellini, Davide
中科院分区：
文献类型：
--
作者：
Gouras, Gunnar K.;Willen, Katarina;Tampellini, Davide
多种证据表明 β-淀粉样蛋白 (Aβ) 与阿尔茨海默病 (AD) 的发病机制有关。然而，Aβ参与疾病过程的机制仍不清楚。 AD 的主要假设是 Aβ 通过分泌的细胞外 Aβ 聚集体的毒性引发疾病。最近，出现了另一种假设，重点关注早期在 AD 易受影响的大脑神经元内积累的 Aβ 库。尽管神经元内 Aβ 的话题一直是该领域的主要关注点，但检测神经元内 Aβ 的技术困难也使得该话题备受争议。在这里，我们回顾了表明神经元内 Aβ 在 AD 中发挥关键作用的证据，并对检测细胞内 Aβ 和 Aβ 的朊病毒样特性所面临的挑战提供了见解。免疫沉淀和蛋白质印迹用于 Aβ 检测。我们强调，标准生化方法可能会低估神经元内 Aβ，而细胞外 Aβ 可以上调细胞内 Aβ。我们还表明去污剂可以去除神经元内的 Aβ。人们越来越认识到神经元内 Aβ 是导致突触功能障碍的关键 Aβ 致病库。检测神经元内 Aβ 的困难不足以成为忽略这一关键 Aβ 池的理由。
Multiple lines of evidence have implicated β-amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD). However, the mechanism(s) whereby Aβ is involved in the disease process remains unclear. The dominant hypothesis in AD has been that Aβ initiates the disease via toxicity from secreted, extracellular Aβ aggregates. More recently, an alternative hypothesis has emerged focusing on a pool of Aβ that accumulates early on within AD vulnerable neurons of the brain. Although the topic of intraneuronal Aβ has been of major interest in the field, technical difficulties in detecting intraneuronal Aβ have also made this topic remarkably controversial. Here we review evidence pointing to the critical role of intraneuronal Aβ in AD and provide insights both into challenges faced in detecting intracellular Aβ and the prion-like properties of Aβ. Immunoprecipitation and Western blot are used for Aβ detection. We highlight that a standard biochemical method can underestimate intraneuronal Aβ and that extracellular Aβ can up-regulate intracellular Aβ. We also show that detergent can remove intraneuronal Aβ. There is a growing awareness that intraneuronal Aβ is a key pathogenic pool of Aβ involved in causing synapse dysfunction. Difficulties in detecting intraneuronal Aβ are an insufficient reason for ignoring this critical pool of Aβ.
登录
查看更多内容
影响因子：
5.5
作者：
Mori, C;Spooner, ET;Lemere, CA
通讯作者：
Lemere, CA
影响因子：
4.2
作者：
Lord, A;Kalimo, H;Nilsson, LNG
通讯作者：
Nilsson, LNG
影响因子：
168.9
作者：
Holmes, Clive;Boche, Delphine;Nicoll, James A. R.
通讯作者：
Nicoll, James A. R.
影响因子：
3.3
作者：
Echeverria, V;Ducatenzeiler, A;Cuello, AC
通讯作者：
Cuello, AC
影响因子：
4.7
作者：
Levi, Ofir;Dolev, Iftach;Michaelson, Daniel M.
通讯作者：
Michaelson, Daniel M.