ICAM-1 protects neurons against Amyloid-β and improves cognitive behaviors in 5xFAD mice by inhibiting NF-Κb
Abstract
Alzheimer's disease (AD) is mainly characterized by amyloid beta (Aβ) plaque deposition and neurofibrillary tangle formation due to tau hyperphosphorylation. It has been shown that astrocytes respond to these pathologies very early and exert either beneficial or deleterious effects towards neurons. Here, we identified soluble intercellular adhesion molecule-1 (ICAM-1) which is rapidly increased in astrocyte conditioned medium derived from Aβ 1-42 treated cultured astrocytes (Aβ 1-42-ACM). Aβ 1-42-ACM was found to be neuroprotective, however, Aβ 1-42-ACM deprived of ICAM-1 was unable to protect neurons against Aβ 1-42 mediated toxicity. Moreover, exogenous ICAM-1 renders protection to neurons from Aβ 1-42 induced death. It blocks Aβ 1-42-mediated PARP cleavage and increases the levels of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, and decreases pro-apoptotic protein Bim. In an Aβ-infused rat model of AD and in 5xFAD mouse, intra-peritoneal administration of ICAM-1 revealed a reduction in Aβ load in hippocampal and cortical regions. Moreover, ICAM-1 treatment led to an increment in the expression of the Aβ-degrading enzyme, neprilysin in 5xFAD mice. Finally, we found that ICAM-1 can ameliorate cognitive deficits in Aβ-infused rat and 5xFAD mouse. Interestingly, ICAM-1 could block the NF-κB upregulation by Aβ and inhibition of NF-κB recovers cognitive impairments in 5xFAD mice. Thus, our study finds a neuroprotective role of ICAM-1 and suggests that it can be a major candidate in cytokine-mediated therapy of AD.
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ICAM-1 plays a role in neuritic plaques on neurite growth and neurodegeneration.
“and this plays a role in neuritic plaques on neurite growth and neurodegeneration [145,146,147].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [147]
ICAM-1, a biomarker of endothelial dysfunction, is increased in Alzheimer's disease, and endothelial cells, astrocytes and microglia show enhanced levels of ICAM-1 in pathological states.
“Experimental evidence confirmed that biomarkers of endothelial dysfunction, such as intercellular adhesion molecule 1 (ICAM-1), are increased in AD; endothelial cells, astrocytes and microglia show enhanced levels of ICAM-1 in pathological states”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [147]
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Self-citation
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Beneficial Effects of Spirulina Consumption on Brain Health
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- Authors
- Guha, S., Paidi, R. K., Goswami, S., Saha, P., & Biswas, S. C.
- Affiliations
- Indian Institute of Chemical Biology (IN)
- Corresponding author
- Biswas, Subhas C.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 100
- Pages
- 194-210
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W4200199820
- Cited by
- 26
- References
- 107
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 1 · 2022: 2
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology, Ministry of Science and Technology, India (BT/PR14383/MED/12/475/2010)
- Council of Scientific and Industrial Research, India
- CSIR-Indian Institute of Chemical Biology
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- ICAM-1, Alzheimer's disease, amyloid-beta, neuroprotection, astrocytes, NF-κB, 5xFAD mice, cognitive impairment, neprilysin, apoptosis, Bcl-2, building information modeling, cytokine therapy, amyloid-beta clearance
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Mice, Transgenic, Neurons, Amyloid beta-Peptides, NF-kappa B, Intercellular Adhesion Molecule-1, Mice, Rats
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