RETRACTED: Chloride intracellular channel 4 blockade improves cognition in mice with Alzheimer's disease: CLIC4 protein expression and tau protein hyperphosphorylation
Abstract
Numerous academic literature suggests that amyloid-β (Aβ) deposition, tau protein phosphorylation, and irreversible neuronal death are the three major causes of AD. The chloride intracellular channel (CLIC) protein family not only regulates the polarisation of neurons, but also has important implications for neuronal survival. Chloride intracellular channel 4 (CLIC4) can be pathologically activated by cyclin-dependent kinase 5 (Cdk5), which causes a significant increase in the expression of CLIC4 and mediates neuronal apoptosis. CLIC4 knockdown inhibits H2O2-induced neuronal apoptosis; however, the relationship between CLIC4 and AD remains unknown. In the present study, we showed that CLIC4 expression was elevated in the hippocampus of AD mice; knockdown of hippocampal CLIC4 alleviated Aβ25-35-induced cognitive impairment in mice; overexpression of hippocampal CLIC4 accelerated Aβ deposition and tau protein hyperphosphorylation in young AD mice (APP/PS1 mice at three months of age). CLIC4 overexpressing mice had a longer escape latency compared to controls in behavioural testing (Morris water maze and T-maze tests). By Co-immunoprecipitation/mass spectrometry (Co-IP/MS) of HT22 cells to identify proteins that specifically bind to CLIC4, we found interactions with CCAAT enhancer binding protein (C/EBPβ); a critical pathway involved in the development of various neurodegenerative diseases. In addition, the knockdown of hippocampal CLIC4 alleviated AD-like pathology by inhibitin…
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Alterations in S100b and CLIC4 occur in AD, and are involved in Aβ clearance and Tau protein binding.
“Alterations in these two indicators of glial activation occur in AD, 64 and are involved in Aβ clearance and Tau protein binding. 64”
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- Authors
- Chen, R., Pan, C., Mao, X., Zhang, Y., Chen, G., Xu, M., Nivar, J., Tao, Y., Cao, H., & Li, J.
- Affiliations
- Wenzhou Medical University (CN)
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Li, Jun
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2024-10
- Volume
- 278
- Issue
- Pt 4
- Pages
- 134972
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W4401827271
- Cited by
- 7
- References
- 20
- Citations by year
- 2026: 3 · 2025: 4
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81771487)
- Wenzhou Medical University (wydw2022-0586)
- Ministry of Science and Technology of the People's Republic of China
- Natural Science Foundation of Zhejiang Province (Y21H090095)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CLIC4, Alzheimer's disease, tau hyperphosphorylation, amyloid-beta, C/EBPβ, hippocampus, cognitive impairment, neuronal apoptosis, APP/PS1 mice, retracted article
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Hippocampus, Male, Mice, Transgenic, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Chloride Channels, Mitochondrial Proteins, Mice, Cognitive Dysfunction
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