Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine, Bryan, TX 77807, USA.
Pharmacol Ther. 2012 Apr;134(1):68-81. doi: 10.1016/j.pharmthera.2011.12.008. Epub 2011 Dec 30.
This review focuses on the neurobiology of integrins, pathophysiological roles of integrins in neuroplasticity and nervous system disorders, and therapeutic implications of integrins as potential drug targets and possible delivery pathways. Neuroplasticity is a central phenomenon in many neurological conditions such as seizures, trauma, and traumatic brain injury. During the course of many brain diseases, in addition to intracellular compartment changes, alterations in non-cell compartments such as extracellular matrix (ECM) are recognized as an essential process in forming and reorganizing neural connections. Integrins are heterodimeric transmembrane receptors that mediate cell-ECM and cell-cell adhesion events. Although the mechanisms of neuroplasticity remain unclear, it has been suggested that integrins undergo plasticity including clustering through interactions with ECM proteins, modulating ion channels, intracellular Ca(2+) and protein kinase signaling, and reorganization of cytoskeletal filaments. As cell surface receptors, integrins are central to the pathophysiology of many brain diseases, such as epilepsy, and are potential targets for the development of new drugs for neurological disorders.
本篇综述聚焦于整合素的神经生物学、整合素在神经可塑性和神经系统疾病中的病理生理作用，以及整合素作为潜在药物靶点和可能的递药途径的治疗意义。神经可塑性是许多神经疾病（如癫痫、创伤和创伤性脑损伤）中的一个核心现象。在许多脑部疾病的发生过程中，除了细胞内隔室变化，细胞外基质（ECM）等非细胞隔室的改变也被认为是形成和重组神经连接的重要过程。整合素是介导细胞-细胞外基质和细胞-细胞黏附事件的异二聚体跨膜受体。尽管神经可塑性的机制尚不清楚，但有研究表明整合素通过与 ECM 蛋白的相互作用发生包括聚集在内的可塑性改变，调节离子通道、细胞内 Ca(2+)和蛋白激酶信号，以及细胞骨架丝的重排。作为细胞表面受体，整合素是许多脑部疾病（如癫痫）病理生理学的核心，也是开发治疗神经障碍新药物的潜在靶点。
