ArticleCell death and differentiation2015
Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 1 of them a synthesis that pooled it.
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Who cites it
181 citing papers in PubMed, 1 synthesis or guideline pooled it, 302 citations in OpenAlex.
- Role of Inflammasomes in Neuroimmune and Neurodegenerative Diseases: A Systematic Review.Mediators of inflammation · 2018Pooled it
- Rare Functional Variants Associated with Antidepressant Remission in Mexican-Americans: Short title: Antidepressant remission and pharmacogenetics in Mexican-Americans.Journal of affective disorders · 2021Trial
- Dietary Supplementation with Omega-3 Fatty Acids Rescues Neurodevelopmental Deficits in a Combined Exposure Paradigm of Maternal Oxycodone Exposure and Chronic Stress.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- NLRP3 inflammasome activation by particles and fibers: implications for human hazard assessment.Archives of toxicology · 2026Review
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- Review
- Neuronal inflammasomes: balancing immunity, neuroinflammation, and homeostasis.Trends in immunology · 2026Review
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- New Perspective: Bench to Bedside Evidence of the Role of CD8+ T Cells in Alzheimer's Disease.Immunity, inflammation and disease · 2026Review
- Optimized detection of caspase-6 activation in a murine inflammation model to inform neurodegenerative disease therapies.PloS one · 2026Article
- Dietary dihydroquercetin alleviates age-related cognitive impairment in association with modulation of apoptosis and pyroptosis pathways.Frontiers in pharmacology · 2026Article
- Screening the optimal rTSMS frequency to orchestrate immune-fibrotic remodeling for adult spinal cord repair.Frontiers in neuroscience · 2026Article
- Parkinson's disease-associated alterations in DNA methylation and hydroxymethylation in human brain.NPJ Parkinson's disease · 2025Article
- The forgotten inflammasomes: AIM2, NLRP1, and NLRC4 in spinal cord injury and neuroinflammation.Inflammopharmacology · 2025Review
- Effects of exercise on neuroinflammation in age-related neurodegenerative disorders.European journal of medical research · 2025Review
- Dual Inhibitors of Acetylcholinesterase and Monoamine Oxidase-B for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Review
- Review
- The Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- Caspase-6/Gasdermin C-Mediated Tumor Cell Pyroptosis Promotes Colorectal Cancer Progression Through CXCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications.Inflammopharmacology · 2025Review
121 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1(-/-) and Casp1(-/-) mice. NLRP1 immunopositive neurons were increased 25- to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-β-mediated neuroinflammation and Casp6-mediated axonal degeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.