ArticleInternational journal of molecular sciences2020
Caspase-6 Knockout in the 5xFAD Model of Alzheimer's Disease Reveals Favorable Outcome on Memory and Neurological Hallmarks.
Article in International journal of molecular sciences, 2020. 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, 32 citations in OpenAlex.
- Optimized detection of caspase-6 activation in a murine inflammation model to inform neurodegenerative disease therapies.PloS one · 2026Article
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- Three decades of caspases and RIPKs in life and death.Human molecular genetics · 2025Review
- Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications.Inflammopharmacology · 2025Review
- The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024Review
- iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.Molecular and cellular neurosciences · 2024Article
- Exploring caspase functions in mouse models.Apoptosis : an international journal on programmed cell death · 2024Review
- Article
- Exploring the significance of caspase-cleaved tau in tauopathies and as a complementary pathology to phospho-tau in Alzheimer's disease: implications for biomarker development and therapeutic targeting.Acta neuropathologica communications · 2024Review
- The neural basis of neuropsychiatric symptoms in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- APP-C31: An Intracellular Promoter of Both Metal-Free and Metal-Bound Amyloid-βAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity.iScience · 2023Article
- Disrupted Maturation of Prefrontal Layer 5 Neuronal Circuits in an Alzheimer's Mouse Model of Amyloid Deposition.Neuroscience bulletin · 2023Article
- Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6.Journal of the American Chemical Society · 2023Article
- c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Qi-fu-yin attenuated cognitive disorders in 5xFAD mice of Alzheimer's disease animal model by regulating immunity.Frontiers in neurology · 2023Article
- Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer's disease.Nature communications · 2022Article
- Neuroprotective Action of Coumarin Derivatives through Activation of TRKB-CREB-BDNF Pathway and Reduction of Caspase Activity in Neuronal Cells Expressing Pro-Aggregated Tau Protein.International journal of molecular sciences · 2022Article
- Apoptotic Pathways and Alzheimer's Disease: Probing Therapeutic Potential.Neurochemical research · 2021Review
- Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma.Cell death discovery · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most common form of dementia in the elderly. Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Caspase-6 is considered to be an up-stream modulator of AD pathogenesis as active caspase-6 is abundant in neuropil threads, neuritic plaques, and neurofibrillary tangles of AD brains. In order to further elucidate the role of caspase-6 activity in the pathogenesis of AD, we produced a double transgenic mouse model, combining the 5xFAD mouse model of AD with caspase-6 knock out (C6-KO) mice. Behavioral examinations of 5xFAD/C6-KO double transgenic mice showed improved performance in spatial learning, memory, and anxiety/risk assessment behavior, as compared to 5xFAD mice. Hippocampal mRNA expression analyses showed significantly reduced levels of inflammatory mediator TNF-α, while the anti-inflammatory cytokine IL-10 was increased in 5xFAD/C6-KO mice. A significant reduction in amyloid-β plaques could be observed and immunohistochemistry analyses showed reduced levels of activated microglia and astrocytes in 5xFAD/C6-KO, compared to 5xFAD mice. Together, these results indicate a substantial role for caspase-6 in the pathology of the 5xFAD model of AD and suggest further validation of caspase-6 as a potential therapeutic target for AD.
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