Glia and semaphorins in neurodegenerative diseases: The frontier for new therapeutics

The optimal development, function, and maintenance of the central nervous system (CNS) are determined by the dynamic and continuous crosstalk between its components. Neurons and glial cells, the cellular constituents of the CNS, orchestrate a wide range of essential activities (Allen and Lyons, 2018). Notably, glial cells, which outnumber neurons, constitute the major population within the CNS. This population comprises astrocytes, microglia, oligodendrocytes, and ependymal cells, each fulfilling specialized functions that contribute to neural homeostasis and overall CNS integrity. Astrocytes are pivotal in preserving structural and functional integrity through the regulation of synaptic function, the clearance of neurotransmitters, and ion balance. Moreover, they provide metabolic support to neurons. Microglia are resident immune cells that provide continuous surveillance within the CNS, regulating brain development and maintenance of neuronal networks. Oligodendrocytes are responsible for myelination, thereby modulating the speed of action potential conduction and optimizing neural communication. Lastly, ependymal cells, which form the epithelial lining of the brain’s ventricular system, are essential for the production of cerebrospinal fluid, its regulation, and the clearance of waste, thus playing a pivotal role in brain metabolism.