The Role of Gasdermin-D-Mediated Pyroptosis in Organ Injury and Its Therapeutic Implications

Figures & data

Table 1. Summary of therapeutic compounds in organ injury targeting pathways leading to GSDMD-mediated pyroptosis.

Organ injury	Disease	Therapies	Target	Reference
Liver	NAFLD/NASH	Jiangzhi Ligan Decoction (JZLGD)	ASC, NLRP3, Caspase-1 and Caspase-11 located upstream of GSDMD	K. Yin et al.^Citation17
Central nervous system	Post-ischemic stroke	VX765	Caspase-1	J Li et al. ^Citation22
	Spinal cord injury	Carbon monoxide release molecule-3 (CORM3)	Inflammasome	J. P. de Rivero Vaccari et al.^Citation34
Cardiovascular	myocardial ischemia/reperfusion injury	Emodin	TLR4/MyD88/NkFB/NLRP3/GSDMDM pathway	B. Ye et al ^Citation23
	Abdominal aortic aneurysm	Difluoromethylornithine (DMFO)	Putrescine synthesis	J. Goa et al. ^Citation24
Lung	Sepsis-induced acute lung injury	Hemin	NLRP3/ASC/Caspase-1	Y. P. Luo et al. ^Citation25
	Sepsis-induced acute lung injury	Corticosteroids	1) NFkB signaling pathway 2) mitochondria ROS dependent NLRP3 activation	J. Yang et al. ^Citation26
	Sepsis-induced acute lung injury	Cyclic helix B peptide	NLRP3, IL1B secretion	P. X. Zhang et al. ^Citation27
	brain injury induced by acute lung injury	Ghrelin	TLR4-NFκB pathway	F X Shao et al. ^Citation28
	Lung vaso-occlusion in sickle cell disease	Z-VAD-FMK	Caspase inhibitor	R. Vats et al. ^Citation29
Kidney	Renal Ischemia-Reperfusion Injury	Parthenolide	NFκB and Tisp40	C. Xiao et al. ^Citation30
Gastrointesinal tract	DSS-induced colitis	cGAS inhibitor RU.521	cGAS signaling pathway	C. Ma et al. ^Citation31
	Ulcerative colitis	Honokiol	TLR4/NFκB	N. Wang et al. ^Citation32

Table 2. Summary of therapeutic compounds in organ injury targeting GSDMD cleavage, IL1β and IL18 release.

Organ injury	Disease	Therapies	Target	Reference
Liver	Severe liver injury	isothiocyanate (PEITC)	NLRP3, Caspase-1, Cystiene 191 of GSDMD	J. Wang et al. ^Citation20
	Acute liver failure induced by Lipopolysaccharide/D-galactosamine	Necrosulfonamide	GSDMD	Wu et al. ^Citation21
Central nervous system	Acute spinal cord injury	Celastrol	NLRP3, ASC, Caspase-1, GSDMD	W. Dai et al. ^Citation50 Xu et al. ^Citation51
Cardiovascular	Acute Myocardial injury	Necrosulfonamide	GSDMD	Wu et al. ^Citation21 K.Jiang et. al ^Citation54
	Ischemic stroke	DL-3-n-butylphthalide (NBP)	GSDMD-NT	B. Han et al. ^Citation55
Lung	Sepsis-induced acute lung injury	Dihydromyricetin (DHM)	NLRP3/caspase-1/IL1β/IL18/GSDMD-NT	Yc. Wang et al. ^Citation56
	Severe acute pancreatitis (SAP)-associated lung injury	Disulfiram	GSDMD, IL1β and IL18 release	J. Wu et al. ^Citation57
	SAP in intestinal injuries	siRNA-GSDMD	GSDMD, IL1β and IL18 release	T. Lin et al. ^Citation58
	Multiple organ dysfunction syndromes	Disulfiram	GSDMD, IL1β and IL18 release	C. Silva et al. ^Citation59
	Lung vaso-occlusion in sickle cell disease	Necrosulfonamide, Disulfiram, LDC7559	GSDMD-NT	R. Vats et al. ^Citation29
Kidney	Cisplatin-induced acute kidney injury	Paricalcitol, a vitamin D receptor agonist	NFκB/NLRP3/cleaved caspase-1/GSDMD	S. Jiang et al. ^Citation60
	Iopromide-induced AKI	Acetylbritannilactone	NLRP3/ASC/GSDMD and release of IL1β and IL18	F. Chen at al. ^Citation61

Figure 1. GSDMD contributes to organ injury regulation through different pathways: caspase-1, ASC and NLRP3; TLR4-NFκB pathway; Gasdermin-D cleavage, IL1β and IL18 release.

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