From the Guidelines

Yes, NLRP3 activation can lead to neurological disorders.

The activation of the NLRP3 inflammasome has been linked to the release of pro-inflammatory cytokines, such as IL-1β and IL-18, which can contribute to neuroinflammation and neuronal damage 1.
In the context of ischemic stroke, NLRP3 activation has been shown to play a key role in the inflammatory response, with increased NLRP3 protein levels and IL-1β and IL-18 expression observed after ischemic stroke 1.
The NLRP3 inflammasome can be activated by various stimuli, including mitochondrial dysfunction, oxidative stress, and the release of danger-associated molecular patterns (DAMPs) such as mtDNA 1.
In chronic pain and depression/anxiety states, the NLRP3 inflammasome can be activated by extracellular ATP, which binds to the microglial P2X7 receptor, leading to the release of pro-inflammatory cytokines and neuroinflammation 1.
Some studies have suggested that inhibiting the NLRP3 inflammasome may be a potential therapeutic strategy for alleviating neuroinflammation and promoting neuroprotection in neurological disorders, such as ischemic stroke and chronic pain 1.

The NLRP3 inflammasome is a multiprotein complex that activates caspase-1, leading to the cleavage of pro-IL-1β and pro-IL-18 and the release of mature IL-1β and IL-18 1.
The activation of the NLRP3 inflammasome can lead to pyroptotic cell death, a form of programmed cell death characterized by the release of pro-inflammatory cytokines and the disruption of the cell membrane 1.
The NLRP3 inflammasome can also interact with other signaling pathways, such as the NF-κB and p38-MAPK pathways, to promote neuroinflammation and neuronal damage 1.

From the Research

The activation of the NLRP3 inflammasome has been linked to the development of neuroinflammation, which is a key contributor to various neurological disorders 2, 3, 4, 5, 6.
The NLRP3 inflammasome is a multiprotein complex that can sense and be activated by a wide range of exogenous and endogenous stimuli, leading to the production of pro-inflammatory cytokines and neuronal damage 2, 3.

The activation of the NLRP3 inflammasome results in the activation of caspase-1, which subsequently leads to the processing of interleukin-1β (IL-1β) and interleukin-18 (IL-18) pro-inflammatory cytokines 2, 3.
These cytokines drive inflammatory responses through diverse downstream signaling pathways, leading to neuronal damage and contributing to the development of neurological disorders 2, 3, 4, 5, 6.

Various therapeutic approaches have been investigated to target the NLRP3 inflammasome, including:
- Anti-IL-1 therapy 2
- Small molecule NLRP3 inhibitors 2, 3
- Cellular and gene therapy 3
- Dietary phytochemicals 6