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配体门控离子通道:对胶质瘤的预后及治疗意义

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.

作者信息

Hey Grace, Rao Rohan, Carter Ashley, Reddy Akshay, Valle Daisy, Patel Anjali, Patel Drashti, Lucke-Wold Brandon, Pomeranz Krummel Daniel, Sengupta Soma

机构信息

College of Medicine, University of Florida, Gainesville, FL 32610, USA.

College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.

出版信息

J Pers Med. 2023 May 19;13(5):853. doi: 10.3390/jpm13050853.

Abstract

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

摘要

胶质瘤是常见的原发性脑恶性肿瘤,由于其整体侵袭性和异质性,治疗仍然困难。尽管已经采用了多种治疗策略来治疗胶质瘤,但越来越多的证据表明,配体门控离子通道(LGICs)在胶质瘤的发病机制中可作为一种有价值的生物标志物和诊断工具。包括P2X、SYT16和PANX2在内的各种LGICs在胶质瘤发病机制中可能发生改变,这会破坏神经元、小胶质细胞和星形胶质细胞的稳态活动,进一步加剧胶质瘤的症状和进展。因此,包括嘌呤受体、谷氨酸门控受体和半胱氨酸环受体在内的LGICs已在临床试验中成为靶点,因其在胶质瘤诊断和治疗中具有潜在的治疗益处。在本综述中,我们讨论了LGICs在胶质瘤发病机制中的作用,包括遗传因素以及LGIC活性改变对神经元细胞生物学功能的影响。此外,我们还讨论了关于将LGICs用作胶质瘤临床靶点和潜在治疗方法的当前及新出现的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/10224160/164cf8fffef6/jpm-13-00853-g002.jpg

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