Molecular Cognition Laboratory, Biophysics Institute, CSIC-UPV/EHU, Campus Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Spain.
Molecular Cognition Laboratory, Biophysics Institute, CSIC-UPV/EHU, Campus Universidad del País Vasco, Barrio Sarriena s/n, 48940 Leioa, Spain; Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neuroscience. 2018 Feb 1;370:81-87. doi: 10.1016/j.neuroscience.2017.10.002. Epub 2017 Oct 10.
The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signaling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory. Lastly, we describe a new peptide derived from the well-known tumor suppressor PTEN that prevents pathological interactions between PTEN and PDZ proteins at synapses during exposure to Amyloid beta. This action prevents memory deterioration in mouse model of Alzheimer's disease. Together, this review indicates how learning and memory can be improved by manipulating synaptic function and number through pharmacological treatment with peptides, and it establishes synaptic function as a valid target for cognitive enhancement.
本文旨在概述三种通过改善突触功能来提高实验动物学习和记忆能力的肽。我们总结了它们的结构、作用机制以及对突触和认知功能的影响。首先，我们描述了源自神经细胞黏附分子的 FGL，它通过激活蛋白激酶 C（PKC）通路来改善认知，该通路触发 AMPA 受体在突触处的活性依赖性传递。然后，我们描述了 PTD4-PI3KAc 肽，它通过激活 PI3K 信号通路促进突触和棘突的形成，并增强海马体依赖的记忆。最后，我们描述了一种源自著名肿瘤抑制因子 PTEN 的新型肽，该肽可防止暴露于淀粉样蛋白β时，PTEN 与 PDZ 蛋白在突触处的病理性相互作用。这种作用可防止阿尔茨海默病小鼠模型的记忆恶化。总的来说，该综述表明，通过使用肽进行药理学治疗来操纵突触功能和数量，可以提高学习和记忆能力，并确立了突触功能作为认知增强的有效靶点。
