The NMDA receptor as a target for cognitive enhancement.
The NMDA receptor as a target for cognitive enhancement.
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DOI：
10.1016/j.neuropharm.2012.06.051
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发表时间：
2013-01
影响因子：
4.7
通讯作者：
Jane DE
中科院分区：
文献类型：
--
作者：
Collingridge GL;Volianskis A;Bannister N;France G;Hanna L;Mercier M;Tidball P;Fang G;Irvine MW;Costa BM;Monaghan DT;Bortolotto ZA;Molnár E;Lodge D;Jane DE
NMDA受体（NMDAR）在神经可塑性中发挥重要作用，包括长期增强和长期抑制，这可能解释了它们在学习和记忆中的重要性。认知能力下降是人口老龄化面临的一个主要问题，因此逆转认知能力下降已成为科学研究和制药开发的一个重要目标。增强NMDAR功能是实现这一目标的核心策略。在这篇综述中，我们指出了通过直接和间接调制增强NMDAR功能的一些主要方法。有充分的证据表明，正调节和负调节都可以增强功能，这表明在特定的临床情况下，需要一种微妙的方法来纠正失衡。需要小心避免过度激活和由此产生的有害影响。最后，我们描述了一些新的NMDARs的正变构调节剂，具有一定的亚基选择性，并显示了它们影响NMDAR介导事件的能力的初步证据。
NMDA receptors (NMDAR) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events.