Caspase-1 and Inflammasome Signaling in Spinal Cord Injury: Mechanistic Insights and Translational Gaps
5 affiliations
- 1Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
- 2Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- 3Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
- 4The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- 5Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Abstract
Caspase-1 is a central mediator of canonical inflammasome signaling and drives neuroinflammatory injury through interleukin-1β (IL-1β) and interleukin-18 (IL-18) maturation, gasdermin D (GSDMD)-mediated pyroptosis, and secondary inflammatory cascades. In spinal cord injury (SCI) and other neurologic disorders, experimental evidence links caspase-1 activation to blood–spinal cord barrier (BSCB) or blood–brain barrier (BBB) disruption, glial activation, neuronal and oligodendroglial injury, and worse functional outcomes. However, despite mechanistic rationale, the clinical role of caspase-1 as a biofluid biomarker remains incompletely defined. This review summarizes preclinical and clinical evidence regarding caspase-1 and inflammasome-associated proteins across cerebrospinal fluid (CSF), serum, plasma, and other biofluids, emphasizing SCI and translational neuroinflammation. Human studies suggest that inflammasome-associated markers may reflect acute inflammatory activity and injury severity, but direct caspase-1 measurement is limited by small cohorts, heterogeneous sampling windows, variable assay platforms, and inconsistent correlations with neurologic outcomes. Overall, caspase-1 remains a biologically plausible but not clinically established biomarker. Future studies should incorporate longitudinal sampling, standardized assays, paired measurement of IL-1β, IL-18, GSDMD, and other pyroptosis-related markers, and integration with imaging and functional outcomes. Such work may clarify whether caspase-1 can serve as a clinically actionable biomarker, prognostic indicator, or therapeutic monitoring target in SCI and related neuroinflammatory conditions.
Related
- Natural Products in Anticancer Activity: 2nd Edition—From Chemical Diversity to Mechanistic and Translational Insights
- Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
- Sulforaphane as a Therapeutic Target for Sarcopenia in Type 2 Diabetes: Mechanistic Insights and Translational Evidence.
- Single-cell Transcriptomics in Autoimmune Diseases: Mechanistic Insights, Cross-disease Convergence, and Translational Challenges in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Type 1 Diabetes, and Multiple Sclerosis.
- TNF-induced lethality occurs independently of NLRP3 inflammasome signaling
BibTeX
@article{cummings2026caspase1,
title = {{Caspase-1 and Inflammasome Signaling in Spinal Cord Injury: Mechanistic Insights and Translational Gaps}},
author = {Adonicah Y. Cummings and Adham M. Khalafallah and Bhavjeet S. Sanghera and Isabella R. Chamma and Emily L. Errante and Adam S. Levy and Hisham F. Bahmad and W. Dalton Dietrich and Juan Pablo de Rivero Vaccari and S. Shelby Burks},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198802},
url = {https://www.mdpi.com/1422-0067/27/19/8802},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Caspase-1 and Inflammasome Signaling in Spinal Cord Injury: Mechanistic Insights and Translational Gaps
AU - Adonicah Y. Cummings
AU - Adham M. Khalafallah
AU - Bhavjeet S. Sanghera
AU - Isabella R. Chamma
AU - Emily L. Errante
AU - Adam S. Levy
AU - Hisham F. Bahmad
AU - W. Dalton Dietrich
AU - Juan Pablo de Rivero Vaccari
AU - S. Shelby Burks
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198802
UR - https://www.mdpi.com/1422-0067/27/19/8802
AB - Caspase-1 is a central mediator of canonical inflammasome signaling and drives neuroinflammatory injury through interleukin-1β (IL-1β) and interleukin-18 (IL-18) maturation, gasdermin D (GSDMD)-mediated pyroptosis, and secondary inflammatory cascades. In spinal cord injury (SCI) and other neurologic disorders, experimental evidence links caspase-1 activation to blood–spinal cord barrier (BSCB) or blood–brain barrier (BBB) disruption, glial activation, neuronal and oligodendroglial injury, and worse functional outcomes. However, despite mechanistic rationale, the clinical role of caspase-1 as a biofluid biomarker remains incompletely defined. This review summarizes preclinical and clinical evidence regarding caspase-1 and inflammasome-associated proteins across cerebrospinal fluid (CSF), serum, plasma, and other biofluids, emphasizing SCI and translational neuroinflammation. Human studies suggest that inflammasome-associated markers may reflect acute inflammatory activity and injury severity, but direct caspase-1 measurement is limited by small cohorts, heterogeneous sampling windows, variable assay platforms, and inconsistent correlations with neurologic outcomes. Overall, caspase-1 remains a biologically plausible but not clinically established biomarker. Future studies should incorporate longitudinal sampling, standardized assays, paired measurement of IL-1β, IL-18, GSDMD, and other pyroptosis-related markers, and integration with imaging and functional outcomes. Such work may clarify whether caspase-1 can serve as a clinically actionable biomarker, prognostic indicator, or therapeutic monitoring target in SCI and related neuroinflammatory conditions.
SN - 1422-0067
ER -