The modulatory role of dopamine receptors in brain neuroinflammation

Abstract

Neuroinflammation is a general pathological feature of central nervous system (CNS) diseases, primarily caused by activation of astrocytes and microglia, as well as the infiltration of peripheral immune cells. Inhibition of neuroinflammation is an important strategy in the treatment of brain disorders. Dopamine (DA) receptor, a significant G protein-coupled receptor (GPCR), is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor families, according to their downstream signaling pathways. Traditionally, DA receptor forms a wide variety of psychological activities and motor functions, such as voluntary movement, working memory and learning. Recently, the role of DA receptor in neuroinflammation has been investigated widely, mainly focusing on nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, renin-angiotensin system, αB-crystallin, as well as invading peripheral immune cells, including T cells, dendritic cells, macrophages and monocytes. This review briefly outlined the functions and signaling pathways of DA receptor subtypes as well as its role in inflammation-related glial cells, and subsequently summarized the mechanisms of DA receptors affecting neuroinflammation. Meaningfully, this article provided a theoretical basis for drug development targeting DA receptors in inflammation-related brain diseases.

Keywords: Dopamine receptor; Glial cell; NLRP3 inflammasome; Neuroinflammation; Peripheral immune cells; Renin-angiotensin system.