The role of dopamine in NLRP3 inflammasome inhibition: Implications for neurodegenerative diseases

In the Central Nervous System (CNS), neuroinflammation orchestrated by microglia and astrocytes is an innate immune response to counteract stressful and dangerous insults. One of the most important and best characterized players in the neuroinflammatory response is the NLRP3 inflammasome, a multiproteic complex composed by NOD-like receptor family Pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and pro-caspase-1. Different stimuli mediate NLRP3 activation, resulting in the NLRP3 inflammasome assembly and the pro-inflammatory cytokine (IL-1 beta and IL-18) maturation and secretion. The persistent and uncontrolled NLRP3 inflammasome activation has a leading role during the pathophysiology of neuroinflammation in age -related neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD). The neurotransmitter dopamine (DA) is one of the players that negatively modulate NLRP3 inflammasome activation through DA receptors expressed in both microglia and astrocytes. This review summarizes recent findings linking the role of DA in the modulation of NLRP3-mediated neuroinflammation in PD and AD, where early deficits of the dopa-minergic system are well characterized. Highlighting the relationship between DA, its glial receptors and the NLRP3-mediated neuroinflammation can provide insights to novel diagnostic strategies in early disease phases and new pharmacological tools to delay the progression of these diseases.

Automated summary

Neuroinflammation in the CNS is an innate immune response involving microglia and astrocytes to counteract insults. The NLRP3 inflammasome plays a key role in the neuroinflammatory response, and its persistent activation is implicated in neurodegenerative diseases like PD and AD. The neurotransmitter dopamine negatively modulates NLRP3 activation, and understanding the relationship between dopamine, glial receptors, and neuroinflammation can lead to novel diagnostic strategies and therapeutic approaches.