Journal
BIOMEDICAL REPORTS
Volume 2, Issue 2, Pages 167-171Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/br.2013.213
Keywords
proprotein convertase subtilisin/kexin type 9; apoptosis; Alzheimer's disease; oxidized low-density lipoprotein; beta-site amyloid precursor protein-cleaving enzyme 1; amyloid beta peptide
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Funding
- National Natural Science Foundation of China [81200217, 81370376]
- Key Project of the Educational Department of Hunan Province [10A105]
- Project of the Health Department of Hunan Province [B2011-042]
- Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province
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Neuronal apoptosis is crucial in neurodegenerative diseases. However, a lower apoptotic rate of nerve cells is detected in the brain compared to that in other organs in neurodegenerative patients or in animal models, suggesting that neuronal apoptosis induced by any type of risk factors is intricately regulated. Human and animal studies demonstrated that a high concentration of oxidized LDL (ox-LDL) in the brain, which is associated with hyperlipidemia, is one of the key apoptosis inducers in neurodegenerative diseases. However, the mechanism underlying the ox-LDL-mediated regulation of neuronal apoptosis has not been fully elucidated. Recently, we investigated proprotein convertase subtilisin.kexin type 9 (PCSK9), a striking gene involved in lipid metabolism that exhibits a positive correlation with macrophage and endothelial cell apoptosis induced by ox-LDL. Moreover, PCSK9 may degrade beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), the key enzyme cleaving amyloid precursor protein (APP) to generate amyloid beta peptide (A beta). A beta is another key apoptosis inducer in neurodegenerative diseases. Our findings indicated that PCSK9 may be upregulated by the high levels of ox-LDL in the brain associated with hyperlipidemia and promote neuronal apoptosis through the NF-kappa B-B-cell lymphoma 2 (Bcl-2)/ Bax-caspase 9-caspase 3 signaling pathways. Moreover, increased PCSK9 levels may inhibit
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