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组蛋白去乙酰化酶抑制剂:改善癌症治疗与降低神经毒性的哥伦布之蛋?

HDACi: The Columbus' Egg in Improving Cancer Treatment and Reducing Neurotoxicity?

作者信息

Squarzoni Angelica, Scuteri Arianna, Cavaletti Guido

机构信息

Experimental Neurology Unit and Milan Center for Neuroscience, School of Medicine and Surgery, Milano-Bicocca University, 20900 Monza, Italy.

PhD Program in Neuroscience, School of Medicine and Surgery, Milano-Bicocca University, 20900 Monza, Italy.

出版信息

Cancers (Basel). 2022 Oct 26;14(21):5251. doi: 10.3390/cancers14215251.

DOI:10.3390/cancers14215251
PMID:36358670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9654569/
Abstract

Histone deacetylases (HDACs) are a group of enzymes that modify gene expression through the lysine acetylation of both histone and non-histone proteins, leading to a broad range of effects on various biological pathways. New insights on this topic broadened the knowledge on their biological activity and even more questions arose from those discoveries. The action of HDACs is versatile in biological pathways and, for this reason, inhibitors of HDACs (HDACis) have been proposed as a way to interfere with HDACs' involvement in tumorigenesis. In 2006, the first HDACi was approved by FDA for the treatment of cutaneous T-cell lymphoma; however, more selective HDACis were recently approved. In this review, we will consider new information on HDACs' expression and their regulation for the treatment of central and peripheral nervous system diseases.

摘要

组蛋白脱乙酰酶(HDACs)是一类通过对组蛋白和非组蛋白进行赖氨酸乙酰化来修饰基因表达的酶,这会对各种生物学途径产生广泛影响。关于这一主题的新见解拓宽了我们对其生物学活性的认识,而这些发现也引发了更多问题。HDACs在生物学途径中的作用具有多样性,因此,HDACs抑制剂(HDACis)被提议作为一种干扰HDACs参与肿瘤发生的方法。2006年,首个HDACi被美国食品药品监督管理局(FDA)批准用于治疗皮肤T细胞淋巴瘤;然而,最近又有更多选择性HDACis获得批准。在本综述中,我们将探讨有关HDACs表达及其调控的新信息,以用于治疗中枢和外周神经系统疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/88d49fdabe42/cancers-14-05251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/6713e51f28ba/cancers-14-05251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/8edc56dc40e6/cancers-14-05251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/88d49fdabe42/cancers-14-05251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/6713e51f28ba/cancers-14-05251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/8edc56dc40e6/cancers-14-05251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d63/9654569/88d49fdabe42/cancers-14-05251-g003.jpg

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Mol Neurobiol. 2022 Oct;59(10):6141-6157. doi: 10.1007/s12035-022-02965-6. Epub 2022 Jul 25.
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Temporal, spatial and molecular pattern of dopaminergic neurodegeneration in the AAV-A53T α-synuclein rat model of Parkinson's disease.帕金森病AAV-A53T α-突触核蛋白大鼠模型中多巴胺能神经变性的时间、空间和分子模式。
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