Targeting Receptor Tyrosine Kinases: Emerging Therapeutic Strategies in Neurodegenerative Disease Management

Neurodegenerative diseases are a group of inherited and sporadic illnesses associated with progressive nervous system dysfunction and neuronal death. For disorders affecting peripheral tissues, protein kinases are a class of pharmacological targets that are gaining popularity. However, due to issues with drug discovery, developing kinase-targeted treatments for disorders affecting the Central Nervous System (CNS) remains challenging. The Receptor Tyrosine Kinases (RTKs) are a class of membrane-bound receptors consisting of an extracellular ligandbinding domain, a transmembrane domain, and an intracellular catalytic domain. Various biological processes, such as growth, differentiation, motility, and metabolism, are reliant on RTKs. The deregulation of receptor tyrosine kinase function plays a significant role in the pathogenesis of various neurodegenerative disorders. The investigation revealed modifications in the Tropomyosin receptor kinase (Trk), Epidermal Growth Factor Receptor 1 (EGFR1), and vascular endothelial growth factor-B (VEGF-B) TAM receptors associated with neurological disorders. Additionally, the data suggest that Receptor Tyrosine Kinases (RTKs) initiate two critical signaling pathways that contribute to neuronal survival and neurite expansion: PI3K/Akt/GSK-3β pathway and Wnt/β-catenin pathway. This chapter outlines the key traits of RTK subdivisions and the associated intraneuronal signaling pathways in various neurodegenerative diseases. It's important to understand the fundamental principles underlying RTKs in neurodegenerative diseases to select the appropriate neuroprotective medication.