A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus.
A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus.
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肽模拟靶向跨性别的NCAM结合位点可促进海马中的空间学习和神经可塑性。
DOI：
10.1371/journal.pone.0023433
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sandi C
中科院分区：
文献类型：
--
作者：
Kraev I;Henneberger C;Rossetti C;Conboy L;Kohler LB;Fantin M;Jennings A;Venero C;Popov V;Rusakov D;Stewart MG;Bock E;Berezin V;Sandi C
神经细胞粘附分子（neural cell adhesion molecule， NCAM）在可塑性和认知中的关键作用，使其成为开发认知增强药物的相关靶点。然而，NCAM是一种结构和功能复杂的分子，具有参与各种作用的多个结构域，这就提出了应该针对哪个NCAM片段的问题。合成的NCAM模拟肽可以模拟与特定相互作用相关的NCAM序列，从而可以识别NCAM中最有希望的靶标。最近，一种NCAM - plannexin的十肽配体被开发出来，作为研究NCAM反式相互作用的工具，它模仿了Ig2中一个亲同型反式结合位点并与ig3结合。在这项研究中，我们研究了plannexin影响神经可塑性和记忆形成的能力。我们发现，无论是在基础条件下，还是在NCAM翻译后可塑性修饰（多涎化）缺失的条件下，plannexin都能促进原代海马神经元培养中神经突的生长，并改善大鼠的空间学习能力。我们还发现plannexin增强海马区CA1的兴奋性突触传递，在那里它还增加了蘑菇棘的数量和AMPAR亚基GluA1和GluA2的突触表达。总之，这些发现提供了令人信服的证据，证明计划蛋白是海马CA1区域突触功能、结构和分子可塑性的重要促进剂，突出了NCAM的Ig3模块中计划蛋白结合的片段，作为开发认知增强药物的新靶点。
The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM. Recently, a decapeptide ligand of NCAM—plannexin, which mimics a homophilic trans-binding site in Ig2 and binds to Ig3—was developed as a tool for studying NCAM's trans-interactions. In this study, we investigated plannexin's ability to affect neural plasticity and memory formation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmission in hippocampal area CA1, where it also increases the number of mushroom spines and the synaptic expression of the AMPAR subunits GluA1 and GluA2. Altogether, these findings provide compelling evidence that plannexin is an important facilitator of synaptic functional, structural and molecular plasticity in the hippocampal CA1 region, highlighting the fragment in NCAM's Ig3 module where plannexin binds as a novel target for the development of cognition-enhancing drugs.
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影响因子：
6.6
作者：
Kohler, Lene B.;Christensen, Claus;Berezin, Vladimir
通讯作者：
Berezin, Vladimir
影响因子：
2.7
作者：
Herrero, Ana I.;Sandi, Carmen;Venero, Cesar
通讯作者：
Venero, Cesar
影响因子：
2.5
作者：
Calandreau, L.;Marquez, C.;Sandi, C.
通讯作者：
Sandi, C.
DOI：
10.1007/978-1-4419-1170-4_9
发表时间：
2010-01-01
期刊：
STRUCTURE AND FUNCTION OF THE NEURAL CELL ADHESION MOLECULE NCAM
影响因子：
--
作者：
El Maarouf, Abderrahman;Rutishauser, Urs
通讯作者：
Rutishauser, Urs
影响因子：
3.3
作者：
BONFANTI, L;OLIVE, S;THEODOSIS, DT
通讯作者：
THEODOSIS, DT