Khan Ariba, Sharma Poonam, Dahiya Sarthak, Sharma Bhupesh
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India.
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India; Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-II, Greater Noida, 201306 Uttar Pradesh, India.
Neurosci Biobehav Rev. 2025 Feb;169:105999. doi: 10.1016/j.neubiorev.2024.105999. Epub 2025 Jan 3.
Plexins are a family of transmembrane receptors known for their diverse roles in neural development, axon guidance, neuronal migration, synaptogenesis, and circuit formation. Semaphorins are a class of secreted and membrane proteins that act as primary ligands for plexin receptors. Semaphorins play a crucial role in central nervous system (CNS) development by regulating processes such as axonal growth, neuronal positioning, and synaptic connectivity. Various types of semaphorins like sema3A, sema4A, sema4C, sema4D, and many more have a crucial role in developing brain diseases. Likewise, various evidence suggests that plexin receptors are of four types: plexin A, plexin B, plexin C, and plexin D. Plexins have emerged as crucial regulators of neurogenesis and neuronal development and connectivity. When bound to semaphorins, these receptors trigger two major networking cascades, namely Rho and Ras GTPase networks. Dysregulation of plexin networking has been implicated in a myriad of brain disorders, including autism spectrum disorder (ASD), Schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD), and many more. This review synthesizes findings from molecular, cellular, and animal model studies to elucidate the mechanisms by which plexins contribute to the pathogenesis of various brain diseases.
丛状蛋白是一类跨膜受体家族，因其在神经发育、轴突导向、神经元迁移、突触形成和神经回路形成中的多种作用而闻名。信号素是一类分泌型和膜蛋白，作为丛状蛋白受体的主要配体发挥作用。信号素通过调节轴突生长、神经元定位和突触连接等过程，在中枢神经系统（CNS）发育中发挥关键作用。各种类型的信号素，如sema3A、sema4A、sema4C、sema4D等等，在脑部疾病的发生发展中起着关键作用。同样，各种证据表明丛状蛋白受体有四种类型：丛状蛋白A、丛状蛋白B、丛状蛋白C和丛状蛋白D。丛状蛋白已成为神经发生、神经元发育和连接的关键调节因子。当与信号素结合时，这些受体触发两个主要的网络级联反应，即Rho和Ras GTPase网络。丛状蛋白网络失调与多种脑部疾病有关，包括自闭症谱系障碍（ASD）、精神分裂症、阿尔茨海默病（AD）、帕金森病（PD）等等。本综述综合了分子、细胞和动物模型研究的结果，以阐明丛状蛋白导致各种脑部疾病发病机制的过程。
