Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice
Abstract
The inflammasome assembles leading to increased cleavage and activity of caspase-1 and downstream IL-1β release, which plays a significant role in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that caspase-1-mediated neuroinflammation occurs early in AD process. However, the detailed role of caspase-1 in aging-related AD-like neuropathology is still unclear so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we detected the levels of caspase-1 in brains of 3-, 7-, and 11-month-old mice and observed that caspase-1 was activated during aging process. More importantly, we provided the evidence that VX-765, a selective inhibitor of caspase-1, significantly rescued spatial learning and memory impairments and reduced tau hyperphosphorylation in brains of SAMP8 mice at early stages of the disease. This amelioration might be attributed to IL-1β-induced hypoactivation of tau kinases. Our results imply that caspase-1 may represent as a potential therapeutic target for neurodegenerative tauopathies.
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Neuroinflammatory readouts such as soluble TREM2, YKL-40, or inflammasome-derived products may provide insight into the immune component of Alzheimer's disease progression.
“Neuroinflammatory readouts such as soluble TREM2, YKL-40, or inflammasome-derived products (e.g., caspase-1 cleavage fragments) may provide insight into the immune component of disease progression [172, 173].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [172]
Cites
NLRP3 inflammasome activation drives tau pathology
Ising, C., Venegas, C., Zhang, S., Scheiblich, H., Schmidt, S. V., Vieira-Saecker, A., Schwartz, S., Albasset, S., McManus, R. M., Tejera, D., et al. (2019) · Nature · doi:10.1038/s41586-019-1769-z · Cited by 1,487 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · cited 1× · see citing works
“Tau therapies are still in early developmental stages (Congdon and Sigurdsson 2018).”
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Tau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
- Authors
- Tan, M.-S., Liu, Y., Hu, H., Tan, C.-C., & Tan, L.
- Affiliations
- Qingdao University (CN)
- Corresponding author
- Tan, Meng-Shan
- Tan, Lan
- Venue
- Metabolic Brain Disease
- Published
- 2022-02-10
- Volume
- 37
- Issue
- 4
- Pages
- 1197-1205
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- OpenAlex
- W4211198456
- Cited by
- 10
- References
- 3
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taishan Scholar Project of Shandong Province (tsqn20161078)
- National Natural Science Foundation of China (81501103, 81771148)
- Distinguished Middle-Aged and Young Scientist Encourage and Reward Foundation of Shandong Province (BS2015SW006)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- caspase-1, tauopathy, Alzheimer's disease, SAMP8 mice, accelerated aging, inflammasome, IL-1β, neuroinflammation, tau hyperphosphorylation, VX-765, spatial learning and memory, tau kinases, cognitive impairment, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Memory Disorders, Caspase 1, Tauopathies, Mice, Cognitive Dysfunction
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