What question did this study set out to answer?

To investigate how the metabolic intermediate fumarate regulates gasdermin D activation and pyroptotic inflammatory cell death.

August 20, 2020ScienceOpen Access

Succination inactivates gasdermin D and blocks pyroptosis

View Full Paper

Ask AI

Bookmark

Authors

FHFiachra HumphriesUMass Memorial Health Care LSLiraz Shmuel-GaliaThe University of Texas Southwestern Medical Center NKNatália Ketelut-CarneiroUMass Memorial Medical Center

Discussion

Member takes

Implication

Preclinical study reveals that fumarate succinates gasdermin D to block pyroptosis in mice, highlighting a therapeutic mechanism for inflammatory diseases.

Key Points

To investigate how the metabolic intermediate fumarate regulates gasdermin D activation and pyroptotic inflammatory cell death.
Assessed the biochemical interaction between endogenous fumarate or dimethyl fumarate (DMF) and gasdermin D (GSDMD) in cell culture models.
Evaluated the in vivo therapeutic efficacy of DMF in mouse models of lipopolysaccharide-induced shock, familial Mediterranean fever, and experimental autoimmune encephalitis.
Fumarate chemically modifies critical cysteine residues on GSDMD through succination, forming S-(2-succinyl)-cysteine.
GSDMD succination blocks caspase binding, cleavage, and oligomerization, thereby preventing lytic cell death.
Administration of DMF suppresses GSDMD-dependent inflammation in mice, protecting against septic shock and attenuating signs of neuroinflammation and autoinflammatory disease.

Cite This Study

Humphries et al. (2020) studied this question.

synapsesocial.com/papers/69df0867d85e58e37b7a0db2 https://doi.org/10.1126/science.abb9818

View Full Paper

Ask AI

Bookmark

Implication

Preclinical study reveals that fumarate succinates gasdermin D to block pyroptosis in mice, highlighting a therapeutic mechanism for inflammatory diseases.

Succination inactivates gasdermin D and blocks pyroptosis

Discussion

Member takes

Implication

Key Points

Cite This Study

Succination inactivates gasdermin D and blocks pyroptosis

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider