Abstract：
The mechanism of action of low-density lipoprotein receptor related protein 4 (LRP4) is mediated largely via the Agrin-LRP4-MuSK signalling pathway in the nervous system. LRP4 contributes to the development of synapses in the peripheral nervous system (PNS). It interacts with signalling molecules such as the amyloid beta-protein precursor (APP) and the wingless type protein (Wnt). Its mechanisms of action are complex and mediated via interaction between the pre-synaptic motor neuron and post-synaptic muscle cell in the PNS, which enhances the development of the neuromuscular junction (NMJ). LRP4 may function differently in the central nervous system (CNS) than in the PNS, where it regulates ATP and glutamate release via astrocytes. It mayaffect the growth and development of the CNS by controlling the energy metabolism. LRP4 interacts with Agrin to maintain dendrite growth and density in the CNS. The goal of this article is to review the current studies involving relevant LRP4 signaling pathways in the nervous system. The review also discusses the clinical and etiological roles of LRP4 in neurological illnesses, such as myasthenia gravis, Alzheimer\'s disease and epilepsy. In this review, we provide a theoretical foundation for the pathogenesis and therapeutic application of LRP4 in neurologic diseases.
摘要：
低密度脂蛋白受体相关蛋白4（LRP4）的作用机制主要通过神经系统中的Agrin-LRP4-MuSK信号通路介导。LRP4有助于周围神经系统（PNS）中突触的发育。它与信号分子如淀粉样β蛋白前体(APP)和无翼型蛋白(Wnt)相互作用。其作用机制复杂，通过PNS中突触前运动神经元和突触后肌细胞之间的相互作用介导，促进神经肌肉接头（NMJ）的发育。LRP4在中枢神经系统（CNS）中的功能可能与在PNS中的功能不同，它通过星形胶质细胞调节ATP和谷氨酸的释放。它可能通过控制能量代谢影响中枢神经系统的生长发育。LRP4与Agrin相互作用以维持CNS中的枝晶生长和密度。本文的目的是回顾目前涉及神经系统相关LRP4信号通路的研究。该综述还讨论了LRP4在神经系统疾病中的临床和病因作用。比如重症肌无力,阿尔茨海默病和癫痫。在这次审查中,为LRP4在神经系统疾病中的发病机制和治疗应用提供理论依据。
