Pharmacological regulation of HIF-1α, RGC death, and glaucoma

IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Current Opinion in Pharmacology Pub Date : 2024-06-18 DOI:10.1016/j.coph.2024.102467
Shahid Husain, Ryan Leveckis
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Abstract

Hypoxia can regulate oxygen-sensitive pathways that could be neuroprotective to compensate for the detrimental effects of low oxygen. However, prolonged hypoxia can activate neurodegenerative pathways. HIF-1α is upregulated/stabilized in hypoxic conditions, promoting alteration of gene expression, and ultimately leading to cell-death. Therefore, regulation of HIF-1α expression pharmacologically is a vital approach to mitigate cell death. In this review, we provide information showing the role of HIF-1α and its associated pathways in ocular retinopathies. We also discuss the beneficial roles of HIF-1α inhibitor, KC7F2, in ocular pathologies. Finally, we provided our own data demonstrating RGC neuroprotection by KC7F2 in glaucomatous animals.

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对 HIF-1α、RGC 死亡和青光眼的药理调节
缺氧可以调节对氧敏感的途径,从而起到保护神经的作用,弥补低氧的有害影响。然而,长期缺氧会激活神经退行性病变途径。HIF-1α 在缺氧条件下上调/稳定,促进基因表达的改变,最终导致细胞死亡。因此,通过药物调节 HIF-1α 的表达是缓解细胞死亡的重要方法。在这篇综述中,我们提供的信息显示了 HIF-1α 及其相关通路在眼部视网膜病变中的作用。我们还讨论了 HIF-1α 抑制剂 KC7F2 在眼部病变中的有益作用。最后,我们提供了自己的数据,证明了 KC7F2 对青光眼动物 RGC 神经的保护作用。
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来源期刊
CiteScore
8.80
自引率
2.50%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.
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