Proteasome regulators: activators and inhibitors.
Proteasome regulators: activators and inhibitors.
复制标题
DOI：
10.2174/092986709787581860
复制
发表时间：
2009
影响因子：
4.1
通讯作者：
Chen CH
中科院分区：
文献类型：
--
作者：
Huang L;Chen CH
这篇小型综述涵盖了蛋白酶体激活剂和抑制剂的药物发现方面。蛋白酶体参与许多重要的细胞功能，例如细胞周期的调节、细胞分化、信号转导途径、适当免疫反应的抗原处理、应激信号传导、炎症反应和细胞凋亡。由于蛋白酶体在细胞功能中的重要性，蛋白酶体的抑制或激活可能成为多种疾病的有用治疗策略。许多蛋白酶体抑制剂已被鉴定，根据其来源可分为两类：化学合成的小分子和源自天然产物的化合物。将蛋白酶体抑制剂开发为临床有用药物的一个成功案例是肽硼酸盐PS341（硼替佐米）被批准用于治疗多发性骨髓瘤。与蛋白酶体抑制剂相比，能够激活或增强蛋白酶体活性的小分子很少见，并且尚未得到充分研究。细胞蛋白酶体激活剂 PA28 的过度表达对亨廷顿病神经元模型细胞表现出有益的作用，这一事实提出了小分子蛋白酶体激活剂可能成为有用的治疗药物的前景。橄榄苦苷（一种小分子蛋白酶体激活剂）对人类成纤维细胞衰老的有益作用也表明蛋白酶体激活剂可能具有开发成抗衰老剂的潜力。
This mini review covers the drug discovery aspect of both proteasome activators and inhibitors. The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. Due to the importance of the proteasome in cellular functions, inhibition or activation of the proteasome could become a useful therapeutic strategy for a variety of diseases. Many proteasome inhibitors have been identified and can be classified into two groups according to their source: chemically synthesized small molecules and compounds derived from natural products. A successful case of developing a proteasome inhibitor as a clinically useful drug is that the peptide boronate, PS341 (Bortezomib), was approved for the treatment of multiple myeloma. In contrast to proteasome inhibitors, small molecules that can activate or enhance proteasome activity are rare and are not well studied. The fact that over-expression of the cellular proteasome activator PA28 exhibited beneficial effects on the Huntington’s disease neuronal model cells raised the prospect that small molecule proteasome activators could become useful therapeutics. The beneficial effect of oleuropein, a small molecule proteasome activator, on senescence of human fibroblasts also suggested that proteasome activators might have the potential to be developed into anti-aging agents.
登录
查看更多内容
影响因子：
4.8
作者：
Breitschopf, K;Zeiher, AM;Dimmeler, S
通讯作者：
Dimmeler, S
DOI：
10.1159/000468685
发表时间：
1993-01-01
期刊：
ENZYME & PROTEIN
影响因子：
--
作者：
DAHLMANN, B;BECHER, B;KUEHN, L
通讯作者：
KUEHN, L
影响因子：
2.1
作者：
Hatabu, T;Hagiwara, M;Sato, K
通讯作者：
Sato, K
影响因子：
4.9
作者：
Holz-Smith, SL;Sun, IC;Chen, CH
通讯作者：
Chen, CH
影响因子：
16.6
作者：
Feling, RH;Buchanan, GO;Fenical, W
通讯作者：
Fenical, W