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cAMP、cGMP 和淀粉样β:记忆形成的三个理想伴侣。

cAMP, cGMP and Amyloid β: Three Ideal Partners for Memory Formation.

机构信息

Department of Experimental Medicine, Section of General Pathology, University of Genoa, Genoa, Italy.

Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

出版信息

Trends Neurosci. 2018 May;41(5):255-266. doi: 10.1016/j.tins.2018.02.001. Epub 2018 Feb 28.

Abstract

cAMP and cGMP are well established second messengers required for long-term potentiation (LTP) and memory formation/consolidation. By contrast, amyloid β (Aβ), mostly known as one of the main culprits for Alzheimer's disease (AD), has received relatively little attention in the context of plasticity and memory. Of note, however, low physiological concentrations of Aβ seem necessary for LTP induction and for memory formation. This should come as no surprise, since hormesis emerged as a central dogma in biology. Additionally, recent evidence indicates that Aβ is one of the downstream effectors for cAMP and cGMP to trigger synaptic plasticity and memory. We argue that these emerging findings depict a new scenario that should change the general view on the amyloidogenic pathway, and that could have significant implications for the understanding of AD and its pharmacological treatment in the future.

摘要

cAMP 和 cGMP 是长时程增强(LTP)和记忆形成/巩固所必需的经典第二信使。相比之下,β 淀粉样蛋白(Aβ)主要被认为是阿尔茨海默病(AD)的主要罪魁祸首之一,但在可塑性和记忆方面却相对较少受到关注。然而,值得注意的是,Aβ 的低生理浓度似乎对于 LTP 的诱导和记忆的形成是必要的。这并不奇怪,因为激效已成为生物学中的一个核心教条。此外,最近的证据表明,Aβ 是 cAMP 和 cGMP 触发突触可塑性和记忆的下游效应物之一。我们认为,这些新出现的发现描绘了一个新的情景,这应该改变人们对淀粉样蛋白途径的普遍看法,并可能对未来理解 AD 及其药物治疗具有重要意义。

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