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Review Article

DYRK1A抑制剂和治疗阿尔茨海默病的前景

卷 30, 期 6, 2023

发表于: 29 August, 2022

页: [669 - 688] 页: 20

弟呕挨: 10.2174/0929867329666220620162018

价格: $65

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摘要

背景:阿尔茨海默病(AD)是一种慢性神经退行性疾病，也是痴呆症的最常见形式，尤其是在老年人中。由于预期寿命的增加，近年来，受这种疾病影响的人数出现了过度增长，给卫生系统造成了严重问题。近年来，研究已经加强，以寻找新的治疗方法，防止疾病的进展。从这个意义上说，最近的研究表明，位于染色体21q22.2上并在唐氏综合征(DS)中过表达的双特异性酪氨酸磷酸化调节激酶1A (DYRK1A)基因可能在DS和AD的发育性脑障碍和早发性神经退行性变、神经元丢失和痴呆中发挥重要作用。抑制DYRK1A可能有助于阻止其过表达的表型效应，因此，是预防年龄相关神经退行性变的潜在治疗策略，包括阿尔茨海默型病理 目的:在这篇综述中，我们探讨了DYRK1A抑制剂作为潜在的抗ad药物的贡献。 方法:在2014年至今的文献中进行检索，以编译包含DYRK1A的IC50值的体外数据集。此外，我们进行了基于体外和硅片数据的构效关系研究。 结果:分子建模和酶动力学研究表明，DYRK1A可能通过其蛋白水解过程，降低其激酶特异性，促进AD病理发展。结论:进一步评估DYRK1A抑制剂可能有助于AD的新治疗方法。

关键词: 阿尔茨海默病，神经退行性变，蛋白激酶，酶动力学，DYRK1A抑制剂，分子对接。

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