Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders.
Ming-Lei GuoSoheil Kazemi RoodsariYan ChengRachael Elizabeth DempseyWenhui HuPublished in: Biomolecules (2023)
During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR/NF-кB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia-neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.
Keyphrases
- nlrp inflammasome
- inflammatory response
- lps induced
- signaling pathway
- neuropathic pain
- reactive oxygen species
- lipopolysaccharide induced
- oxidative stress
- drug induced
- cell death
- toll like receptor
- poor prognosis
- emergency department
- immune response
- epithelial mesenchymal transition
- high intensity
- white matter
- cognitive impairment
- binding protein
- long non coding rna
- small molecule
- resting state
- regulatory t cells