GSDMD Protein <table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">GSDMD Protein</th>
</tr>
<tr>
<td class="label">
Protein Name </td>
<td>GSDMD (Gasdermin D)</td>
</tr>
<tr>
<td class="label">
Gene Symbol </td>
<td>GSDMD</td>
</tr>
<tr>
<td class="label">
Chromosomal Location </td>
<td>8p22</td>
</tr>
<tr>
<td class="label">
UniProt ID </td>
<td>Q8NHS0</td>
</tr>
<tr>
<td class="label">
Molecular Weight </td>
<td>~56 kDa (full-length)</td>
</tr>
<tr>
<td class="label">
Protein Length </td>
<td>484 amino acids</td>
</tr>
<tr>
<td class="label">
Subcellular Localization </td>
<td>Cytoplasm</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Agent</td>
</tr>
<tr>
<td class="label">GSDMD Inhibitors</td>
<td>Disulfiram</td>
</tr>
<tr>
<td class="label">GSDMD Inhibitors</td>
<td>Dimethyl fumarate</td>
</tr>
<tr>
<td class="label">Caspase-1 Inhibitors</td>
<td>VX-765</td>
</tr>
<tr>
<td class="label">Anti-inflammatory</td>
<td>IL-1β blockade</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas
...
GSDMD Protein <table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">GSDMD Protein</th>
</tr>
<tr>
<td class="label">
Protein Name </td>
<td>GSDMD (Gasdermin D)</td>
</tr>
<tr>
<td class="label">
Gene Symbol </td>
<td>GSDMD</td>
</tr>
<tr>
<td class="label">
Chromosomal Location </td>
<td>8p22</td>
</tr>
<tr>
<td class="label">
UniProt ID </td>
<td>Q8NHS0</td>
</tr>
<tr>
<td class="label">
Molecular Weight </td>
<td>~56 kDa (full-length)</td>
</tr>
<tr>
<td class="label">
Protein Length </td>
<td>484 amino acids</td>
</tr>
<tr>
<td class="label">
Subcellular Localization </td>
<td>Cytoplasm</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Agent</td>
</tr>
<tr>
<td class="label">GSDMD Inhibitors</td>
<td>Disulfiram</td>
</tr>
<tr>
<td class="label">GSDMD Inhibitors</td>
<td>Dimethyl fumarate</td>
</tr>
<tr>
<td class="label">Caspase-1 Inhibitors</td>
<td>VX-765</td>
</tr>
<tr>
<td class="label">Anti-inflammatory</td>
<td>IL-1β blockade</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">331 edges</a></td>
</tr>
</table>
Introduction Gsdmd Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview GSDMD (Gasdermin D) is a critical executioner of pyroptotic cell death. This protein is cleaved by inflammatory caspases (caspase-1, caspase-4/5 in humans, caspase-11 in mice) to release its N-terminal domain, which forms pores in the plasma membrane. These pores cause cell swelling, release of inflammatory cytokines, and ultimately cell death. GSDMD has emerged as a key player in neurodegenerative diseases, linking inflammasome activation to neuronal loss. [@liu2020]
Structure GSDMD contains:
N-terminal Domain (1-275 aa): Forms pores in membrane (gasdermin-N)C-terminal Domain (276-484 aa): Auto-inhibitory domain (gasdermin-C)Linker Region : Recognition site for caspase cleavage (D275↓)Molecular Function
Pyroptosis Execution
Full-length GSDMD is cytosolic and autoinhibited by C-terminal domain binding
Caspase cleavage at D275 separates N- and C-terminal domains
N-terminal domain oligomerizes and inserts into phospholipid membranes
Forms pores (10-20 nm diameter) causing membrane permeabilization
Inflammatory Release
Pores allow release of IL-1β, IL-18, and alarmins (HMGB1, IL-1α)
Enables release of intracellular proteins without complete lysis
Alternative Activation
Can be activated by caspase-3 in certain contexts
Cross-talk with [apoptosis](/entities/apoptosis) pathways
Role in Disease
Alzheimer's Disease
GSDMD-mediated pyroptosis contributes to neuronal loss
Amyloid-β activates [NLRP3](/entities/nlrp3-inflammasome) inflammasome leading to GSDMD cleavage
Microglial pyroptosis propagates neuroinflammation
Blocking GSDMD protects [neurons](/entities/neurons) in vitro
Parkinson's Disease
GSDMD activation in dopaminergic neurons
Mitochondrial toxins (MPTP, 6-OHDA) induce GSDMD-dependent death
[α-Synuclein](/proteins/alpha-synuclein) oligomers trigger inflammasome → GSDMD pathway
Animal models show protection with GSDMD inhibition
Amyotrophic Lateral Sclerosis
Motor neuron degeneration involves GSDMD-mediated pyroptosis
SOD1 and FUS mutations linked to pyroptotic pathways
[TDP-43](/proteins/tdp-43) pathology associated with inflammasome activation
Stroke and TBI
Ischemic injury triggers GSDMD-dependent neuronal death
Promising therapeutic target for acute brain injury
Therapeutic Targeting
Biomarkers
GSDMD cleavage fragments in CSF and plasma
Caspase-1 activity assays
Pyroptotic cell death markers
Key Publications
Shi J, et al. (2015). Cleavage of GSDMD determines pyroptotic cell death. Nature. 526(7575):660-665.
Liu Z, et al. (2020). Gasdermin D in Alzheimer's disease. J Neuroinflammation. 17(1):234.
Wang Y, et al. (2021). GSDMD in Parkinson's disease. Cell Death Discov. 7(1):202.
Ding J, et al. (2016). Pyroptosis: gasdermin-mediated cell death. Trends Biochem Sci. 42(4):245-254.
Background The study of Gsdmd Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
GSDMD Gene
Pyroptosis Pathway
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome) Caspase-1
External Links
[UniProt: GSDMD](https://www.uniprot.org/uniprot/Q8NHS0)
[NCBI Protein: GSDMD](https://www.ncbi.nlm.nih.gov/protein/Q8NHS0)
[GeneCards: GSDMD](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GSDMD)
References
Shi J, et al, (2015) (2015)
Liu Z, et al, (2020) (2020)
Wang Y, et al, (2021) (2021)
Ding J, et al, (2016) (2016)
Tan Y, et al, (2020) (2020) Show full description