Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies

Abstract

In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders and painful conditions have therefore been successfully identified, including receptors and enzymes, and mediators of neuroinflammation. However, the translation of these promising data to a clinical setting is often hampered by both technical and biological difficulties, making it necessary to perform experiments on human cells and models of the various diseases. In this review we will, therefore, summarize the most relevant data on the contribution of glial cells to human pathologies and on their possible pharmacological modulation based on data obtained in post-mortem tissues and in iPSC-derived human brain cells and organoids. The possibility of an in vivo visualization of glia reaction to neuroinflammation in patients will be also discussed.

Role of Glial Cells in Depression and Drug Addiction

“…It is not surprising, therefore, that their disruption or dysregulation can lead to neuropsychiatric and neurodegenerative diseases [50][104] [119][120][121][122][123]. Indeed, recent developments suggest potential novel interventions in neurodegenerative diseases by targeting glial receptors and enzymes [124]. We have recently proposed that glial nAChRs may be a suitable target for intervention in Parkinson's disease (PD) [123].…”

“…However, emerging evidence suggests that differences in microglia functions are not driven exclusively by their milieu, but rather by the unique properties they possess. Therefore, it is suggested that microglial subtype categorization be based on their function [124][136] [137].…”

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

“…They constantly survey the environment through rapid movements of their fine filopodia, allowing them to react quickly to any kind of insult. Lately, it has been shown that the action of filopodia is cAMP-dependent [ 136 ]. Microglia are considered the immunocompetent and phagocytic cells of the nervous system and share the same origin and express many common cellular markers with peripheral macrophages.…”