Abstract:
C-Jun-N-terminal-kinases (JNKs), members of the mitogen-activated-protein-kinase family, are significantly linked with neurological and neurodegenerative pathologies and cancer progression. However, JNKs serve key roles under physiological conditions, particularly within the central-nervous-system (CNS), where they are critical in governing neural proliferation and differentiation during both embryogenesis and adult stages. These processes control the development of CNS, avoiding neurodevelopment disorders. JNK are key to maintain the proper activity of neural-stem-cells (NSC) and neural-progenitors (NPC) that exist in adults, which keep the convenient brain plasticity and homeostasis. This review underscores how the interaction of JNK with upstream and downstream molecules acts as a regulatory mechanism to manage the self-renewal capacity and differentiation of NSC/NPC during CNS development and in adult neurogenic niches. Evidence suggests that JNK is reliant on non-canonical Wnt components, Fbw7-ubiquitin-ligase, and WDR62-scaffold-protein, regulating substrates such as transcription factors and cytoskeletal proteins. Therefore, understanding which pathways and molecules interact with JNK will bring knowledge on how JNK activation orchestrates neuronal processes that occur in CNS development and brain disorders.
摘要:
C-Jun-N末端激酶(JNKs),丝裂原活化蛋白激酶家族的成员,与神经和神经退行性病变以及癌症进展密切相关。然而,JNK在生理条件下发挥关键作用,特别是在中枢神经系统(CNS)内,在胚胎发生和成年阶段,它们对控制神经增殖和分化至关重要。这些过程控制着中枢神经系统的发展,避免神经发育障碍。JNK是维持成人中存在的神经干细胞(NSC)和神经祖细胞(NPC)的适当活性的关键。保持大脑的可塑性和稳态。这篇评论强调了JNK与上游和下游分子的相互作用如何充当调节机制,以管理CNS发育过程中和成人神经源性壁龛中NSC/NPC的自我更新能力和分化。有证据表明JNK依赖于非规范的Wnt组件,Fbw7-泛素连接酶,和WDR62-支架蛋白,调节底物,如转录因子和细胞骨架蛋白。因此,了解哪些途径和分子与JNK相互作用将带来关于JNK激活如何协调中枢神经系统发育和脑部疾病中发生的神经元过程的知识。