Although the precise mechanism by which the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is activated remains unknown, several stress-related cellular processes, including cytosolic depletion of potassium, lysosome disruption, mitochondrial damage, and intracellular calcium elevation, have been proposed to be involved in the activation of this inflammasome. The NACHT, LRR, and pyrin (PYD) domain-containing protein 3, NLRP3 inflammasome is implicated in both gut immune homeostasis and neuroinflammation, and activation has been found to exacerbate Aβ deposition and cognitive impairment in AD. The neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate the neuroinflammatory response. The NLRP3 inflammasome plays a key role in the inflammatory response of the central system. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, cause neuroprotective effects and thus reduce dementia.

This Special Issue focuses on the search for natural or newly synthesized inhibitors which could inhibit NLRP3 inflammasome complex formation and improve synapse and memory dysfunction. In this Special Issue, we welcome high-quality original research and review articles on the mechanisms of NLRP3 activation and inhibition and its association with dementia and neurodegenerative disease.

Potential topics include but are not limited to the following:

• The mechanism of oxidative stress-mediated NLRP3 activation/inhibition
• The mechanisms for oxidative stress-induced glial cell activation/inhibition leading to neurodegenerative diseases
• The molecular mechanism of new drugs involved in the regulation of oxidative stress and neuroinflammation in the context of neurodegenerative diseases
• Isolating/testing/screening strategies for the discovery of novel anti-brain ageing medicinal agents
• Mechanistic approaches to avoid NLRP3 complex association or to disintegrate the complex into its non-toxic components
• Any newly designed inhibitor(s) that may highly interact with the structural integrity of the complex, dissociate its various connections and abolish its final products