Apolipoprotein J in Alzheimer’s disease: shedding light on its role with cell signaling pathway perspective and possible therapeutic approaches
Abstract
Apolipoprotein J (ApoJ), or clusterin, is one of the main apolipoproteins in the brain. It is synthesized and released from astrocytes in a healthy brain, and its expression increases in neurodegenerative disorders. Genetic evidence has suggested an association between ApoJ polymorphism and the risk of Alzheimer's disease (AD)-it is now considered the third main genetic risk factor for late-onset AD. However, the role of ApoJ overexpression in the state of disorder, toxicity, or protection is not yet clear. Since ApoJ plays different roles in AD, we review the function of ApoJ using different cell signaling pathways in AD and outline its paradoxical roles in AD. ApoJ helps in amyloid-beta (Aβ) clearance. Vice versa, ApoJ gene knock-out causes fibrillary Aβ reduction and prevents Aβ-induced neuron cell death. Understanding ApoJ, through various cellular signaling pathways, creates a new perspective on AD's cellular principles. The overall message is that ApoJ can be a valuable tool in controlling AD.
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ApoJ is one of the main apolipoproteins in the brain and its expression is reported to be upregulated in AD.
“ApoJ is one of the main apolipoproteins in the brain and its expression is reported to be upregulated in AD (48).”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [48]
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Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes
Komai, M., Noda, Y., Ikeda, A., Kaneshiro, N., Kamikubo, Y., Sakurai, T., Uehara, T., & Takasugi, N. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100510 · Cited by 13 · see citing works
- Authors
- Moezzi, S.-M.-I., Mozafari, N., Fazel-Hoseini, S.-M., Nadimi-Parashkoohi, S., Abbasi, H., Ashrafi, H., & Azadi, A.
- Affiliations
- Shiraz University of Medical Sciences (IR)
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Corresponding author
- Azadi, Amir
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-11-30
- Volume
- 11
- Issue
- 24
- Pages
- 4060-4072
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W3109478649
- Cited by
- 13
- References
- 8
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2
- FWCI
- 0.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- clusterin, Alzheimer's disease, amyloid-beta clearance, amyloid-beta fibrillation, signaling pathways, astrocytes, genetic risk factors, late-onset Alzheimer's disease, neuroprotection, therapeutic target
- MeSH terms
- Alzheimer Disease, Apolipoproteins E, Humans, Signal Transduction, Amyloid beta-Peptides, Clusterin
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