An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis
Open accessAbstract
Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course and regulation of target genes is poorly understood. By using a brain-biased array of over 7,500 cDNAs, we profiled this gene expression component of PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined potassium and serum withdrawal, and kainic acid administration. We found that hundreds of genes were significantly regulated in discreet waves including known genes whose protein products are involved in PCD. A restricted set of genes was regulated by all models, providing evidence that signals inducing PCD can regulate large assemblages of genes (of which a restricted subset may be shared in multiple pathways).
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PCSK9 expression can be induced by apoptotic stimulus together with known apoptosis mediators such as death receptor-6 and caspase-3.
“PCSK9 is known to bind to both receptors via the EGF-A repeat of their ectodomains and to target them for degradation, while the expression of PCSK9 can be induced by apoptotic stimulus together with known apoptosis mediators such as death receptor-6 and caspase-3 [4,44].”
From PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling (2012) · cites this paper as [44]
The paper reports that caspase 3 and DR6 expression were regulated in three models of programmed cell death in cerebellar granule neurons. Our copy does not identify PCSK9 as one of the regulated genes or report that an apoptotic stimulus induces its expression (searched: PCSK9, NARC-1, and proprotein convertase). (LLM, conf=0.84)
Experimental — accuracy not yet measuredPCSK9 binds to both VLDLR and ApoER2 via the EGF-A repeat of their ectodomains and targets them for degradation.
“PCSK9 is known to bind to both receptors via the EGF-A repeat of their ectodomains and to target them for degradation, while the expression of PCSK9 can be induced by apoptotic stimulus together with known apoptosis mediators such as death receptor-6 and caspase-3 [4,44].”
From PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling (2012) · cites this paper as [44]
The gene-expression passage (‡ Accession nos.; page not provided) reports regulation of caspase-3 and DR6 during neuronal programmed cell death, but does not address the quoted receptor-binding claim. Searches for PCSK9, VLDLR, ApoER2, EGF-A, and receptor degradation found no passage describing PCSK9 binding to or degrading either receptor. (LLM, conf=0.77)
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Research works printed but not linked: 4
- D'Mello, S. R., Galli, C., Ciotti, T. & Calissano, P. (1993) Proc. Natl. Acad. Sci. USA 90, 10989-10993.
- Everitt, B. S. (1993) Cluster Analysis (Oxford Univ. Press, New York).
- Voehringer, D. W., Hirschberg, D. L., Xiao, J., Lu, Q., Roederer, M., Lock, C. B., Herzenberg, L. A., Steinman, L. & Herzenberg, L. A. (2000) Proc. Natl. Acad. Sci. USA 97, 2680-2685.
- Arabie, P., Hubert, L. J. & De Soete, G. (World Scientific Publishing Co., Singapore), pp. 341-375.
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RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
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RetractedPCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling
Kysenius, K., Muggalla, P., Mätlik, K., Arumäe, U., & Huttunen, H. J. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0977-6 · Cited by 137 · see citing works
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PCSK9 and the nervous system: a no-brainer?
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Zheng, X., Yuan, W., Li, L., Ma, H., Zhu, M., Li, X., & Feng, X. (2025) · European Journal of Medical Research · doi:10.1186/s40001-025-02937-1 · Cited by 9 · see citing works
- Authors
- Chiang, L. W., Grenier, J. M., Ettwiller, L., Jenkins, L. P., Ficenec, D., Martin, J., Jin, F., DiStefano, P. S., & Wood, A.
- Affiliations
- Takeda Oncology (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-02-27
- Volume
- 98
- Issue
- 5
- Pages
- 2814-2819
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC30222
- OpenAlex
- W2082276962
- Cited by
- 108
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- gene expression profiling, cerebellar granule cells, serum deprivation, kainic acid, de novo RNA synthesis, excitotoxicity
- MeSH terms
- Algorithms, Animals, Cells, Cultured, Neurons, Nucleic Acid Hybridization, Apoptosis, DNA, Complementary, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Rats
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