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Review Article

Rho激酶（ROCK）抑制剂-以眼部效用为重点的神经保护疗法范例

卷 27, 期 14, 2020

页: [2222 - 2256] 页: 35

弟呕挨: 10.2174/0929867325666181031102829

价格: $65

摘要

背景：青光眼是一种进行性视神经病变，会导致视力障碍和视网膜神经节细胞（RGC）死亡，因此逐渐需要采取神经保护策略以最大程度减少RGC和视野的损失。它被认为是一种多因素疾病，眼内压（IOP）是最主要的危险因素。已针对各种可能的适应症，例如心肌缺血，高血压，肾脏疾病，对ROCK抑制剂进行了研究。已经表明它们在神经保护和神经元再生中的作用是 在治疗脊髓损伤，阿尔茨海默氏病和多发性硬化等神经系统疾病中具有重要价值，但最近与Rho相关的激酶抑制剂被认为是潜在的抗青光眼药物。 证据：Rho激酶是一种丝氨酸/苏氨酸激酶，具有一个激酶结构域，具有结构活性，参与调节平滑肌收缩和应激纤维形成。已经鉴定出Rho激酶的两种同工型，ROCK-I（ROCK_）和ROCK-II（ROCK_）。 ROCK II在青光眼中具有病理生理作用，因此ROCK的抑制剂可能有助于减轻视力。这些抑制剂通过增加通过小梁网状通路的房水流出而降低了青光眼的眼内压。它们还用作抗瘢痕形成剂，因此可防止青光眼滤过术后的术后瘢痕形成。他们的主要作用涉及 通过增加视神经血流量来再生轴突，这可能对治疗受损的视神经元有用。这些药物直接作用于中央视觉通路的神经元，中断RGC的细胞凋亡，因此可作为一种新型药理药物 青光眼神经保护的方法。 结论：基于高通量筛选的结果，已设计和开发了几种Rho激酶抑制剂，包括多种支架，这些支架在微摩尔至亚纳摩尔范围内均具有Rho激酶抑制活性。脚手架的这种多样性 在本综述中将详细介绍该激酶及其SAR发育的潜在抑制作用。利帕舒地尔是迄今为止市场上用于治疗青光眼的唯一Rho激酶抑制剂。另一款ROCK抑制剂AR-13324最近通过了临床试验 而AMA0076，K115，PG324，Y39983和RKI-983仍在试用中。有鉴于此，本综述将讨论ROCK II抑制剂作为青光眼的下一代治疗剂的详细和更新说明。

关键词: 青光眼，眼压，Rho激酶抑制剂，小梁网，神经保护，利帕舒地。

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