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肽基脯氨酰异构酶Pin1在癫痫神经元信号传导中的作用。

The role of peptidyl-prolyl isomerase Pin1 in neuronal signaling in epilepsy.

作者信息

Chen Yuwen, Hou Xiaojun, Pang Jiao, Yang Fan, Li Angcheng, Lin Suijin, Lin Na, Lee Tae Ho, Liu Hekun

机构信息

Institute of Basic Medicine, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China.

出版信息

Front Mol Neurosci. 2022 Oct 11;15:1006419. doi: 10.3389/fnmol.2022.1006419. eCollection 2022.

DOI:10.3389/fnmol.2022.1006419
PMID:36304997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9592815/
Abstract

Epilepsy is a common symptom of many neurological disorders and can lead to neuronal damage that plays a major role in seizure-related disability. The peptidyl-prolyl isomerase Pin1 has wide-ranging influences on the occurrence and development of neurological diseases. It has also been suggested that Pin1 acts on epileptic inhibition, and the molecular mechanism has recently been reported. In this review, we primarily focus on research concerning the mechanisms and functions of Pin1 in neurons. In addition, we highlight the significance and potential applications of Pin1 in neuronal diseases, especially epilepsy. We also discuss the molecular mechanisms by which Pin1 controls synapses, ion channels and neuronal signaling pathways to modulate epileptic susceptibility. Since neurotransmitters and some neuronal signaling pathways, such as Notch1 and PI3K/Akt, are vital to the nervous system, the role of Pin1 in epilepsy is discussed in the context of the CaMKII-AMPA receptor axis, PSD-95-NMDA receptor axis, NL2/gephyrin-GABA receptor signaling, and Notch1 and PI3K/Akt pathways. The effect of Pin1 on the progression of epilepsy in animal models is discussed as well. This information will lead to a better understanding of Pin1 signaling pathways in epilepsy and may facilitate development of new therapeutic strategies.

摘要

癫痫是许多神经系统疾病的常见症状,可导致神经元损伤,而这种损伤在与癫痫发作相关的残疾中起主要作用。肽基脯氨酰顺反异构酶Pin1对神经疾病的发生和发展具有广泛影响。也有研究表明Pin1作用于癫痫抑制,且其分子机制最近已有报道。在本综述中,我们主要关注关于Pin1在神经元中的机制和功能的研究。此外,我们强调了Pin1在神经元疾病,尤其是癫痫中的意义和潜在应用。我们还讨论了Pin1通过控制突触、离子通道和神经元信号通路来调节癫痫易感性的分子机制。由于神经递质和一些神经元信号通路,如Notch1和PI3K/Akt,对神经系统至关重要,因此在CaMKII-AMPA受体轴、PSD-95-NMDA受体轴、NL2/gephyrin-GABA受体信号传导以及Notch1和PI3K/Akt通路的背景下讨论了Pin1在癫痫中的作用。还讨论了Pin1对动物模型中癫痫进展的影响。这些信息将有助于更好地理解癫痫中Pin1信号通路,并可能促进新治疗策略的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b19/9592815/58e8e8654546/fnmol-15-1006419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b19/9592815/029f080cfed8/fnmol-15-1006419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b19/9592815/58e8e8654546/fnmol-15-1006419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b19/9592815/029f080cfed8/fnmol-15-1006419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b19/9592815/58e8e8654546/fnmol-15-1006419-g002.jpg

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2
Resveratrol attenuates atherosclerotic endothelial injury through the Pin1/Notch1 pathway.白藜芦醇通过 Pin1/Notch1 通路减轻动脉粥样硬化内皮损伤。
Toxicol Appl Pharmacol. 2022 Jul 1;446:116047. doi: 10.1016/j.taap.2022.116047. Epub 2022 May 5.
3
Seizure activity triggers tau hyperphosphorylation and amyloidogenic pathways.癫痫活动触发 tau 过度磷酸化和淀粉样蛋白形成途径。
Cell Stress Chaperones. 2023 Nov;28(6):599-619. doi: 10.1007/s12192-023-01378-1. Epub 2023 Sep 27.
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Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony.tau 减少对兴奋性和抑制性神经元的影响不同,降低了兴奋/抑制比,并对抗了网络过度同步。
Cell Rep. 2021 Oct 19;37(3):109855. doi: 10.1016/j.celrep.2021.109855.
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GABRB2, a key player in neuropsychiatric disorders and beyond.GABRB2,神经精神疾病领域的关键角色。
Gene. 2022 Jan 30;809:146021. doi: 10.1016/j.gene.2021.146021. Epub 2021 Oct 19.
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Biallelic gephyrin variants lead to impaired GABAergic inhibition in a patient with developmental and epileptic encephalopathy.双等位基因甘氨酸受体相关蛋白变异导致一名患有发育性和癫痫性脑病的患者的γ-氨基丁酸能抑制受损。
Hum Mol Genet. 2022 Mar 21;31(6):901-913. doi: 10.1093/hmg/ddab298.
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JCI Insight. 2021 Sep 8;6(17):e151835. doi: 10.1172/jci.insight.151835.
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