Plexins: Navigating through the neural regulation and brain pathology

Abstract

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.