Microglia, one of the glial cells of the central nervous system, has received much attention for its important role in neuroinflammation. Many translational studies are currently underway to discover new drugs that target microglia to treat various central nervous system diseases such as Alzheimer's disease, Parkinson's disease, and depression. Recent studies have shown that histamine in the brain, a neurotransmitter essential for the regulation of various brain functions, regulates glial cells and neurons. In vitro studies using primary microglia and microglial cell lines have reported that histamine receptors are expressed in microglia and regulate microglial functions such as chemotaxis, migration, cytokine secretion and autophagy. In vivo studies have shown that histamine-related reagents can reduce abnormal symptoms in animal models of human diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia. Several human studies have revealed altered histamine receptor levels in amyotrophic lateral sclerosis and Parkinson's disease, suggesting central nervous system histamine, including histamine-dependent microglial regulation, as therapeutic targets for these disorders. Emphasizes the importance of systems.

Finally, abnormal histamine and ATP signaling in the brain has been reported in neurodegenerative/neuroinflammatory diseases such as multiple sclerosis, Alzheimer's disease and Parkinson's disease, and histamine- and ATP-related compounds are currently involved in the same pathologies. is under clinical investigation. Regarding amyotrophic lateral sclerosis, new data on purinergic mechanisms are available, but the involvement of histamine is essentially unexplored. Thus, the evidence presented here provides a solid background for formulating new hypotheses, stimulating  scientific debate, and most importantly, inspiring future research.