Lynx1 prototoxins: critical accessory proteins of neuronal nicotinic acetylcholine receptors.

Lynx1 prototoxins: critical accessory proteins of neuronal nicotinic acetylcholine receptors.
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Lynx1原毒素:神经元烟碱乙酰胆碱受体的关键辅助蛋白。

DOI:
10.1016/j.coph.2020.09.016
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发表时间:
2021-03
影响因子:
4
通讯作者:
Miwa JM
Miwa JM
中科院分区:
医学3区
文献类型:
--
作者:
Miwa JM

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胆碱能系统的烟碱受体是配体门控离子通道,响应于兴奋性神经递质乙酰胆碱和烟草的成瘾成分尼古丁。它们通过激活正常和疾病状态下的特定神经回路来帮助识别环境中的显著信息。虽然烟碱受体是有希望的神经和神经精神疾病靶点,但在几次后期临床失败后,它们已经失宠。靶向烟碱受体的复合物,包括lynx1辅助蛋白,可能是解锁难治性nAChR用于治疗开发的关键。Lynx1结合到nAChR的细胞外表面,并作为一个关键的调节剂,抑制记忆,学习和可塑性。在动物模型中去除Lynx1会导致记忆和可塑性增强,其中一些对神经精神和神经系统疾病具有治疗意义。综述lynx1辅助调制器及其在调节神经元nAChRs的作用将进行讨论。
Nicotinic receptors of the cholinergic system are ligand-gated ion channels, responding to the excitatory neurotransmitter, acetylcholine, and the addictive component of tobacco, nicotine. They help to transduce salient information in the environment by activating specific neural circuitry in normal and disease states. While nicotinic receptors are promising neurological and neuropsychiatric disorder targets, they have fallen out of favor after several late-stage clinical failures. Targeting the complex of the nicotinic receptor, including lynx1 accessory proteins, could be the key to unlocking the intractable nAChR for therapeutic development. Lynx1 binds to the extracellular face of the nAChR and acts as a critical modulator, suppressing memory, learning, and plasticity. Lynx1 removal in animal models leads to memory and plasticity enhancements, some of which have therapeutic relevance for neuropsychiatric and neurological disease. A review of the lynx1 accessory modulator and its role in modulating neuronal nAChRs will be discussed.
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