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靶向热休克蛋白90用于胶质母细胞瘤和神经退行性疾病联合治疗策略的天然产物

Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.

作者信息

Mitra Sarmistha, Dash Raju, Munni Yeasmin Akter, Selsi Nusrat Jahan, Akter Nasrin, Uddin Md Nazim, Mazumder Kishor, Moon Il Soo

机构信息

Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Republic of Korea.

Product Development Department, Popular Pharmaceuticals Ltd., Dhaka 1207, Bangladesh.

出版信息

Metabolites. 2022 Nov 21;12(11):1153. doi: 10.3390/metabo12111153.

Abstract

Glioblastoma multiforme (GBM) is one of the most common aggressive, resistant, and invasive primary brain tumors that share neurodegenerative actions, resembling many neurodegenerative diseases. Although multiple conventional approaches, including chemoradiation, are more frequent in GBM therapy, these approaches are ineffective in extending the mean survival rate and are associated with various side effects, including neurodegeneration. This review proposes an alternative strategy for managing GBM and neurodegeneration by targeting heat shock protein 90 (Hsp90). Hsp90 is a well-known molecular chaperone that plays essential roles in maintaining and stabilizing protein folding to degradation in protein homeostasis and modulates signaling in cancer and neurodegeneration by regulating many client protein substrates. The therapeutic benefits of Hsp90 inhibition are well-known for several malignancies, and recent evidence highlights that Hsp90 inhibitors potentially inhibit the aggressiveness of GBM, increasing the sensitivity of conventional treatment and providing neuroprotection in various neurodegenerative diseases. Herein, the overview of Hsp90 modulation in GBM and neurodegeneration progress has been discussed with a summary of recent outcomes on Hsp90 inhibition in various GBM models and neurodegeneration. Particular emphasis is also given to natural Hsp90 inhibitors that have been evidenced to show dual protection in both GBM and neurodegeneration.

摘要

多形性胶质母细胞瘤(GBM)是最常见的侵袭性、耐药性和浸润性原发性脑肿瘤之一,具有神经退行性作用,类似于许多神经退行性疾病。尽管包括放化疗在内的多种传统方法在GBM治疗中更为常用,但这些方法在延长平均生存率方面无效,并且会引发包括神经退行性变在内的各种副作用。本综述提出了一种通过靶向热休克蛋白90(Hsp90)来治疗GBM和神经退行性变的替代策略。Hsp90是一种著名的分子伴侣,在蛋白质稳态中维持和稳定蛋白质折叠直至降解过程中发挥重要作用,并通过调节许多客户蛋白底物来调节癌症和神经退行性变中的信号传导。Hsp90抑制的治疗益处已在多种恶性肿瘤中得到证实,最近的证据表明,Hsp90抑制剂可能抑制GBM的侵袭性,提高传统治疗的敏感性,并在各种神经退行性疾病中提供神经保护作用。在此,本文讨论了Hsp90在GBM和神经退行性变进展中的调节概述,并总结了Hsp90抑制剂在各种GBM模型和神经退行性变中的最新研究结果。还特别强调了天然Hsp90抑制剂,已证明其在GBM和神经退行性变中均具有双重保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13de/9697676/649bfdc446b8/metabolites-12-01153-g001.jpg

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