The ubiquitin-proteasome system (UPS) mediated protein degradation is crucial to maintain quantitive and functional homeostasis of diverse proteins. Balanced cellular protein homeostasis controlled by UPS is fundamental to normal neurological functions while impairment of UPS can also lead to some neurodevelopmental and neurodegenerative disorders. Functioning as the substrate recognition component of the SCF-type E3 ubiquitin ligase, FBXW7 is essential to multiple aspects of cellular processes via targeting a wide range of substrates for proteasome-mediated degradation. Accumulated evidence shows that FBXW7 is fundamental to neurological functions and especially implicated in neurodevelopment and the nosogenesis of neurodegeneration. In this review, we describe general features of FBXW7 gene and proteins, and mainly present recent findings that highlight the vital roles and molecular mechanisms of FBXW7 in neurodevelopment such as neurogenesis, myelination and cerebral vasculogenesis and in the pathogenesis of some typical neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Additionally, we also provide a prospect on focusing FBXW7 as a potential therapeutic target to rescue neurodevelopmental and neurodegenerative impairment.

中文翻译：

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FBXW7 在神经发育和神经退行性疾病中的意义：分子机制和治疗潜力。

泛素-蛋白酶体系统 (UPS) 介导的蛋白质降解对于维持不同蛋白质的定量和功能稳态至关重要。由 UPS 控制的平衡细胞蛋白质稳态是正常神经功能的基础，而 UPS 受损也会导致一些神经发育和神经退行性疾病。作为 SCF 型 E3 泛素连接酶的底物识别组分，FBXW7 通过针对蛋白酶体介导的降解的广泛底物，对细胞过程的多个方面至关重要。累积的证据表明 FBXW7 是神经功能的基础，尤其与神经发育和神经退行性疾病的发病机制有关。在这篇综述中，我们描述了 FBXW7 基因和蛋白质的一般特征，并主要介绍最近的发现，这些发现强调了 FBXW7 在神经发育（如神经发生、髓鞘形成和脑血管发生）以及一些典型神经退行性疾病（如阿尔茨海默病、帕金森病和亨廷顿病）的发病机制中的重要作用和分子机制。此外，我们还提供了将 FBXW7 作为潜在治疗靶点以挽救神经发育和神经退行性障碍的前景。