Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.
Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.
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DOI：
10.3389/fncel.2015.00191
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发表时间：
2015
影响因子：
5.3
通讯作者：
De Felice FG
中科院分区：
文献类型：
--
作者：
Ferreira ST;Lourenco MV;Oliveira MM;De Felice FG
阿尔茨海默病（AD）是老年人中最常见的痴呆症，影响着全世界数百万人。随着发达国家和发展中国家阿尔茨海默病病例数量的持续增加，寻找有效阻止或逆转疾病进展的治疗方法构成了一项重大的研究和公共卫生挑战。由于确定了淀粉样蛋白β肽（a β）是AD大脑中典型的淀粉样斑块的主要成分，因此主要的努力旨在确定a β是否以及如何导致记忆丧失和认知障碍。在过去15年中积累的大量证据支持可溶性Aβ寡聚物（Aβ o）在AD的突触失效和神经元功能障碍中起关键作用。尽管如此，一些基本问题，包括突触毒性寡聚物的确切分子组成，它们所结合的受体的身份，以及最终导致突触失效的信号通路，仍然没有明确的答案。在这里，我们讨论了最近的进展，这些进展阐明了我们对有毒物质的化学性质及其对突触的有害影响的理解，并最终提出了阿尔茨海默病发病机制的Aβ寡聚物假说。我们还强调了阿尔茨海默病研究中应该解决的突出问题和挑战，以便将研究成果转化为有效的阿尔茨海默病治疗方法。
Alzheimer’s disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-β peptide (Aβ) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Aβ leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Aβ oligomers (AβOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Aβ oligomer hypothesis for Alzheimer’s pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies.
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DOI：
10.1523/jneurosci.1729-12.2012
发表时间：
2012-10-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cameron B;Tse W;Lamb R;Li X;Lamb BT;Landreth GE
通讯作者：
Landreth GE
影响因子：
5.3
作者：
Brouillette, Jonathan;Caillierez, Raphaelle;Buee, Luc
通讯作者：
Buee, Luc
DOI：
10.1111/j.1532-5415.2011.03365.x
发表时间：
2011-05-01
影响因子：
6.3
作者：
Brodaty, Henry;Breteler, Monique M. B.;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
15.1
作者：
Bjorklund NL;Reese LC;Sadagoparamanujam VM;Ghirardi V;Woltjer RL;Taglialatela G
通讯作者：
Taglialatela G
影响因子：
5.3
作者：
Abisambra, Jose F.;Jinwal, Umesh K.;Dickey, Chad A.
通讯作者：
Dickey, Chad A.