Photo Credit: Selvanegra

The following is a summary of  “LRP4-related signaling pathways and their regulatory role in neurological diseases,” published in the December 2023 issue of Neurology by Chen et al.

Low-density lipoprotein receptor-related protein 4 (LRP4) operates predominantly through the Agrin-LRP4-MuSK signaling pathway within the nervous system, exerting a pivotal role in synaptic development in the peripheral nervous system (PNS). Its intricate mechanisms involve interactions with essential signaling molecules like the amyloid beta-protein precursor (APP) and the wingless-type protein (Wnt). Within the PNS, LRP4’s actions are complex, fostering connections between pre-synaptic motor neurons and post-synaptic muscle cells to facilitate the formation and maturation of the neuromuscular junction (NMJ).

While its role in the PNS is established, LRP4 might function differently within the central nervous system (CNS). In CNS contexts, LRP4’s potential activities encompass the regulation of ATP and glutamate release via astrocytes, influencing CNS growth and development by modulating energy metabolism. Moreover, LRP4’s interaction with Agrin in the CNS plays a vital role in maintaining dendrite growth and density.

This study aims to comprehensively review current research elucidating the intricate signaling pathways associated with LRP4 within the nervous system. Additionally, it delves into the clinical implications and etiological roles of LRP4 in various neurological disorders, including myasthenia gravis, Alzheimer’s disease, and epilepsy. By synthesizing existing studies, this review strives to lay a theoretical foundation that sheds light on the pathogenesis of neurological diseases involving LRP4 and explores the potential therapeutic applications of targeting LRP4 pathways in these conditions.

Understanding the multifaceted actions of LRP4 in the nervous system is crucial for unraveling its roles in neurological disorders. This comprehensive review seeks to bridge the gap in current knowledge, providing valuable insights into the mechanisms by which LRP4 influences neurological processes. By elucidating these pathways and their relevance to clinical conditions, this review aims to offer a conceptual framework for the potential therapeutic manipulation of LRP4 in treating and managing various neurological diseases.

Source: sciencedirect.com/science/article/abs/pii/S0006899323004766