TABLE 1.

Direct NLRP3 inhibitors as potential Parkinson’s disease (PD) therapeutics at pre-clinical stages.

Target category	Inflammasome component	Direct NLRP3 inhibitors	Mechanism of inhibition	Current CNS models
Sensor	NLRP3	MCC950	Blocks ATPase activity Locks NLRP3 in inactive state (Coll et al., 2015, 2019)	MPTP-induced mice (Huang et al., 2021) α-synuclein PFF–injected mice (Gordon et al., 2018) MitoPark mice (Gordon et al., 2018) 6-OHDA-lesioned mice (Gordon et al., 2018)
		CY-09	Blocks ATPase activity Binds NACHT region of NLRP3 (Jiang W. et al., 2017)	Stroke mice (Sun et al., 2020)
		Bay 11-7082	Blocks ATPase activity (Juliana et al., 2010) Unknown binding site	Spinal cord injury mice (Jiang W. et al., 2017)
		OLT1177	Blocks ATPase activity (Marchetti et al., 2018) Unknown binding site	Alzheimer’s disease mice (Lonnemann et al., 2020) Experimental autoimmune encephalomyelitis (Sanchez-Fernandez et al., 2019)
		Oridonin	Attenuates NLRP3-NEK7 interaction Binds Cys279 (NACHT domain) (He et al., 2018)	Traumatic brain injury mice (Zhao et al., 2022)
		RRx-001	Attenuates NLRP3-NEK7 interaction Binds Cys409 (NACHT domain) (Chen Y. et al., 2021)	Experimental autoimmune encephalomyelitis mice (Chen Y. et al., 2021)
		JC-171	Attenuates NLRP3-ASC (Guo et al., 2017)	Experimental autoimmune encephalomyelitis (Guo et al., 2017)
Effectors	Caspase-1	VX-765	Reduce caspase-1-induced α-synuclein aggregation (Wang et al., 2016)	Multiple system atrophy (MSA) mice (Bassil et al., 2016) Alzheimer mice (Flores et al., 2020)
	Gasdermin D	Dimethyl fumarate	Succinates C191 Blocks GSDMD oligomerization (Yadav et al., 2021)	Experimental autoimmune encephalomyelitis mice (Yadav et al., 2021)