ArticleJCI insight2023
Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Baicalein alleviates Alzheimer's disease pathology in AD models by activating the PI3K/AKT/GSK3β pathway to inhibit neuronal apoptosis.Scientific reports · 2026Article
- Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026Review
- Article
- Inflammasome-Mediated Neuroinflammation: A Key Driver in Alzheimer's Disease Pathogenesis.Biomolecules · 2025Review
- Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications.Inflammopharmacology · 2025Review
- Asrij/OCIAD1 depletion reduces inflammatory microglial activation and ameliorates Aβ pathology in an Alzheimer's disease mouse model.Journal of neuroinflammation · 2025Article
- Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells.Cellular & molecular biology letters · 2024Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Caspases in Alzheimer's Disease: Mechanism of Activation, Role, and Potential Treatment.Molecular neurobiology · 2024Review
- Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.International journal of molecular sciences · 2024Review
- RIPK3 signaling and its role in regulated cell death and diseases.Cell death discovery · 2024Review
- RIPK3 promotes islet amyloid-induced β-cell loss and glucose intolerance in a humanized mouse model of type 2 diabetes.Molecular metabolism · 2024Article
- Inflammasomes in neurological disorders - mechanisms and therapeutic potential.Nature reviews. Neurology · 2024Review
- Article
- Article
- Role of NLRP3 Inflammasomes in Neurodegenerative Diseases.The Eurasian journal of medicine · 2023Article
- Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model.Scientific reports · 2023Article
- The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Inflammasome assembly in neurodegenerative diseases.Trends in neurosciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular mediators of cell death and inflammation in Alzheimer's disease (AD) have yet to be fully elucidated. Caspase-8 is a critical regulator of several cell death and inflammatory pathways; however, its role in AD pathogenesis has not yet been examined in detail. In the absence of caspase-8, mice are embryonic lethal due to excessive receptor interacting protein kinase 3-dependent (RIPK3-dependent) necroptosis. Compound RIPK3 and caspase-8 mutants rescue embryonic lethality, which we leveraged to examine the roles of these pathways in an amyloid β-mediated (Aβ-mediated) mouse model of AD. We found that combined deletion of caspase-8 and RIPK3, but not RIPK3 alone, led to diminished Aβ deposition and microgliosis in the mouse model of AD carrying human presenilin 1 and amyloid precursor protein with 5 familial AD mutations (5xFAD). Despite its well-known role in cell death, caspase-8 did not appear to affect cell loss in the 5xFAD model. In contrast, we found that caspase-8 was a critical regulator of Aβ-driven inflammasome gene expression and IL-1β release. Interestingly, loss of RIPK3 had only a modest effect on disease progression, suggesting that inhibition of necroptosis or RIPK3-mediated cytokine pathways is not critical during midstages of Aβ amyloidosis. These findings suggest that therapeutics targeting caspase-8 may represent a novel strategy to limit Aβ amyloidosis and neuroinflammation in AD.
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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 Socratic graph.