ArticleHuman molecular genetics2016
The human-specific CASP4 gene product contributes to Alzheimer-related synaptic and behavioural deficits.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- AI Accelerated Chemical Screening Integrates ChemBERTa to Identify Repositionable CASP4 Inhibitors via MD Simulations and MM/PBSA Analysis.Journal of chemical information and modeling · 2026Article
- Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Article
- Porphyromonas gingivalis outer membrane vesicles divert host innate immunity and promote inflammation via C4' monophosphorylated lipid A.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Caspase-4 in glioma indicates deterioration and unfavorable prognosis by affecting tumor cell proliferation and immune cell recruitment.Scientific reports · 2024Article
- DNA hypomethylation promotes the expression of CASPASE-4 which exacerbates inflammation and amyloid-β deposition in Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Decoding sTREM2: its impact on Alzheimer's disease - a comprehensive review of mechanisms and implications.Frontiers in aging neuroscience · 2024Review
- Article
- Molecular Mechanisms of IL18 in Disease.International journal of molecular sciences · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Pyroptosis in Alzheimer's disease: cell type-specific activation in microglia, astrocytes and neurons.Acta neuropathologica · 2023Article
- Interdisciplinary Approaches to Deal with Alzheimer's Disease-From Bench to Bedside: What Feasible Options Do Already Exist Today?Biomedicines · 2022Review
- Identification of hub genes in the subacute spinal cord injury in rats.BMC neuroscience · 2022Article
- Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease.Frontiers in pharmacology · 2022Review
- TREM2 ectodomain and its soluble form in Alzheimer's disease.Journal of neuroinflammation · 2020Review
- Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases.Cancers · 2020Article
- Caspase 4 Overexpression as a Prognostic Marker in Clear Cell Renal Cell Carcinoma: A Study Based on the Cancer Genome Atlas Data Mining.Frontiers in genetics · 2020Article
- GJA1 (connexin43) is a key regulator of Alzheimer's disease pathogenesis.Acta neuropathologica communications · 2018Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent studies have indicated that innate immune signalling molecules are involved in late-onset Alzheimer's disease (LOAD) risk. Amyloid beta (Aβ) accumulates in AD brain, and has been proposed to act as a trigger of innate immune responses. Caspase-4 is an important part of the innate immune response. We recently characterized transgenic mice carrying human CASP4, and observed that the mice manifested profound innate immune responses to lipopolysaccharide (LPS). Since these inflammatory processes are important in the aetiology of AD, we have now analysed the correlation of expression of caspase-4 in human brain with AD risk genes, and studied caspase-4 effects on AD-related phenotypes in APPswe/PS1deltaE9 (APP/PS1) mice. We observed that the expression of caspase-4 was strongly correlated with AD risk genes including TYROBP, TREM2, CR1, PSEN1, MS4A4A and MS4A6A in LOAD brains. Caspase-4 expression was upregulated in CASP4/APP/PS1 mice in a region-specific manner, including hippocampus and prefrontal cortex. In APP/PS1 mice, caspase-4 expression led to impairments in the reversal phase of a Barnes maze task and in hippocampal synaptic plasticity, without affecting soluble or aggregated Aβ levels. Caspase-4 was expressed predominantly in microglial cells, and in the presence of CASP4, more microglia were clustered around amyloid plaques. Furthermore, our data indicated that caspase-4 modulates microglial cells in a manner that increases proinflammatory processes. We propose that microglial caspase-4 expression contributes to the cognitive impairments in AD, and that further study of caspase-4 will enhance our understanding of AD pathogenesis and may lead to novel therapeutic targets in AD.
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