Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325000, China.
Protein Cell. 2022 Jan;13(1):6-25. doi: 10.1007/s13238-020-00812-9. Epub 2020 Dec 11.
The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.
丝氨酸/苏氨酸蛋白激酶 21（p21-activated kinases，PAKs）作为 Rho GTP 酶 Cdc42 和 Rac 的主要效应物，是将复杂的细胞骨架网络与广泛的神经活动联系起来的重要分子开关群。PAKs 在大脑中有广泛的表达，但在特定的细胞类型、脑区和发育阶段存在差异。PAKs 在控制神经细胞骨架重塑方面发挥着重要且不同的作用，与神经元的发育和命运以及树突棘的结构和功能可塑性有关。PAK 介导的肌动蛋白信号转导和相互作用的功能网络是多种神经发育和神经退行性疾病中经常受到影响的共同途径。鉴于针对 PAK 的特异性小分子激动剂和抑制剂已在癌症治疗中得到开发，全面了解 PAK 在神经细胞骨架重塑中的作用将有助于我们理解神经疾病背后的复杂机制，这也可能成为这些疾病的潜在治疗靶点。
