CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits
Open accessAbstract
Reactive astrogliosis and early synaptic degeneration are 2 characteristic hallmarks in Alzheimer's disease (AD) brains, but a direct link between the 2 events has not been established. Here, we show that cancerous inhibitor of PP2A (CIP2A), a cancerous protein with high expression level in astrocytes, is upregulated in patients with AD and 3xTg-AD transgenic mice. Overexpression of CIP2A in astrocytes through adeno-associated virus infection both in cultured cells and in mice brains results in activation of astrocytes, increased production of cytokines and Aβ, and synaptic degeneration indicated by decreased levels of synaptic proteins, spine loss, and impairment in long-term potentiation. As a result of synaptic degeneration, CIP2A overexpression in astrocytes in vivo induces significant deficits in visual episodic memory detected by novel objective recognition test and spatial memory detected by Morris water maze. We conclude that CIP2A-promoted astrogliosis induces synaptic degeneration and cognitive deficits in AD.
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CIP2A is strongly implicated in Alzheimer's disease via regulation of both Tau and APP.
“As CIP2A is also strongly implicated in Alzheimer´s disease via regulation of both Tau and APP32,58”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [58]
The Introduction and Results (page not available in our copy) link CIP2A to Alzheimer’s disease and report increased Aβ production after CIP2A overexpression in astrocytes. They do not show CIP2A regulating Tau or APP; increased Aβ production alone does not establish regulation of APP. (LLM, conf=0.88)
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- Authors
- Shentu, Y.-P., Hu, W.-T., Zhang, Q., Huo, Y., Liang, J.-W., Liuyang, Z.-Y., Zhou, H., Wei, H., Ke, D., Wang, X.-C., Wang, J.-Z., Man, H.-Y., Westermarck, J., & Liu, R.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Boston University (US)
- Åbo Akademi University (FI)
- Corresponding author
- Liu, Rong
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 75
- Pages
- 198-208
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC6405315
- OpenAlex
- W2904944085
- Cited by
- 21
- References
- 34
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 5
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China, China (81471304, 31771189)
- Natural Science Foundation of Hubei Province (2017CFA065)
- NIH, United States (R01MH079407)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CIP2A, astrocyte activation, Alzheimer's disease, synaptic degeneration, astrocytes, cognitive impairment, amyloid-beta, cytokines, long-term potentiation, 3xTg-AD mice, visual episodic memory, spatial memory, adeno-associated virus overexpression
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Autoantigens, Cognition, Cognition Disorders, Disease Models, Animal, Hippocampus, Membrane Proteins, Memory Disorders, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Long-Term Potentiation, Cognitive Dysfunction, Spatial Memory
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