在阿尔茨海默病实验模型中靶向突触可塑性
Targeting Synaptic Plasticity in Experimental Models of Alzheimer's Disease.
作者信息
Mango Dalila, Saidi Amira, Cisale Giusy Ylenia, Feligioni Marco, Corbo Massimo, Nisticò Robert
机构信息
Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, Italy.
Department of Physiology and Pharmacology, Sapienza University of Rome, Italy.
出版信息
Front Pharmacol. 2019 Jul 16;10:778. doi: 10.3389/fphar.2019.00778. eCollection 2019.
Abstract
Long-term potentiation (LTP) and long-term depression (LTD) of hippocampal synaptic transmission represent the principal experimental models underlying learning and memory. Alterations of synaptic plasticity are observed in several neurodegenerative disorders, including Alzheimer's disease (AD). Indeed, synaptic dysfunction is an early event in AD, making it an attractive therapeutic target for pharmaceutical intervention. To date, intensive investigations have characterized hippocampal synaptic transmission, LTP, and LTD in and in murine models of AD. In this review, we describe the synaptic alterations across the main AD models generated so far. We then examine the clinical perspective of LTP/LTD studies and discuss the limitations of non-clinical models and how to improve their predictive validity in the drug discovery process.
摘要
海马体突触传递的长时程增强（LTP）和长时程抑制（LTD）是学习和记忆的主要实验模型。在包括阿尔茨海默病（AD）在内的几种神经退行性疾病中，都观察到了突触可塑性的改变。事实上，突触功能障碍是AD的早期事件，这使其成为药物干预的一个有吸引力的治疗靶点。迄今为止，深入的研究已经对AD患者和AD小鼠模型中的海马体突触传递、LTP和LTD进行了表征。在这篇综述中，我们描述了迄今为止所产生的主要AD模型中的突触改变。然后，我们审视了LTP/LTD研究的临床前景，并讨论了非临床模型的局限性以及如何在药物发现过程中提高其预测效度。
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