核分布因子同源蛋白1在神经元分化中的调控作用

The regulatory role of nuclear distribution element-like 1 in neuronal differentiation

摘要:

核分布因子同源蛋白1（NDEL1）是一种在神经发育过程中发挥多重调控功能的关键蛋白，广泛参与神经元分化、神经突生长、微管动力学调控及神经元迁移等过程。近年来，越来越多的研究揭示了NDEL1通过多层级调控机制介导神经元发育及其在神经系统疾病中的潜在作用。该文系统总结了NDEL1在神经元分化过程中的分子机制，包括通过miR-103-3p等miRNA的负向调控、与无脑回畸形蛋白1和精神分裂症易感基因1等蛋白的相互作用，以及NDEL1对Wnt/β-catenin信号通路的正调控作用。此外， NDEL1的酶活性及其与精神分裂症易感基因1–束状延伸蛋白zeta-1复合物的相互作用对神经突形成与稳定至关重要。值得关注的是，NDEL1在病理状态下亦发挥重要作用。综上，NDEL1不仅是调控神经元发育的重要因子，也可能在神经精神疾病中发挥关键作用。深入阐明NDEL1相关分子网络与信号通路的交叉机制，将有助于推动神经发育与神经精神疾病研究的发展，并为靶向干预提供新思路。

Abstract:

Nuclear distribution element-like 1 （NDEL1） is a key regulator protein that plays multifaceted roles in neurodevelopment， and it is involved in various processes such as neuronal differentiation， neurite outgrowth， microtubule dynamics， and neuronal migration. In recent years， an increasing number of evidence has shown that NDEL1 mediates neuron development through multilayered regulatory mechanisms and may play a role in various neurological disorders. This article systematically reviews the molecular mechanisms of NDEL1 in neuronal differentiation， including its negative regulation by miRNAs such as miR-103-3p， its interactions with the proteins such as lissencephaly-1 protein and disrupted in schizophrenia 1 （DISC1）， and its positive modulation of the Wnt/β-catenin signaling pathway. Moreover， the enzymatic activity of NDEL1 and its interaction with the DISC1-fasciculation and elongation protein zeta-1 complex are crucial for neurite formation and stability. Notably， NDEL1 also plays an important role under pathological conditions. In summary， NDEL1 is a critical regulator of neuronal development and may play an important role in neuropsychiatric diseases. Further clarification of NDEL1-centered molecular networks and crosstalk among signaling pathways will promote the research on neurodevelopment and neuropsychiatric diseases and provide new ideas for targeted intervention.