Molecular Cloning of a Novel Apoptosis-Related Gene, Human Nap1 (NCKAP1), and Its Possible Relation to Alzheimer Disease
Abstract
Expression profiles of thousands of genes (cDNAs) were analyzed in sporadic Alzheimer disease (AD)-affected brains in comparison with normal subjects by using the high-density cDNA filter method and differential display analysis. Among 31 differentially expressed genes, one gene was found to be markedly depressed in AD-affected brains. A full-length (or nearly full-length) cDNA of the gene was isolated and sequenced. The cDNA turned out to be an orthologue of rat Nap1. The gene was thus designated human Nap1 (HGMW-approved symbol NCKAP1) and was mapped to human chromosome 2q32 by fluorescence in situ hybridization. Northern blotting and in situ hybridization studies showed that in brain, the gene is predominantly expressed in neuronal cells. Antisense oligo DNA of human Nap1 transcripts was found to induce apoptosis of neuronal cells. Based on these results, the possible role of human Nap1 in AD is discussed.
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NCKAP1 expression was discovered to be markedly reduced in the brains of AD patients compared with those of normal subjects.
“NCKAP1 expression was also discovered to be markedly reduced in the brains of AD patients compared with those of normal subjects152, but the functional roles of NCKAP1 downregulation in AD remain to be established.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [152]
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Candidate gene for the chromosome 1 familial Alzheimer’s disease locus
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Apoptosis in neurodegenerative disorders
Mattson, M. P. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35040009 · Cited by 1,605 · see citing works
Kunda, P., Craig, G., Dominguez, V., & Baum, B. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.005 · Cited by 341 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Suzuki, T., Nishiyama, K., Yamamoto, A., Inazawa, J., Iwaki, T., Yamada, T., Kanazawa, I., & Sakaki, Y.
- Affiliations
- Nagoya City University (JP)
- The University of Tokyo (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Kyushu University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Suzuki, Takashi
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 63
- Issue
- 2
- Pages
- 246-254
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2078282095
- Cited by
- 66
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Corporation
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- NCKAP1, NAP1, Alzheimer's disease, apoptosis, neuronal apoptosis, gene expression profiling, differential gene expression, antisense oligonucleotides, neurons, cDNA cloning
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amino Acid Sequence, Animals, Base Sequence, Brain, Cloning, Molecular, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Proteins, RNA, Messenger, Gene Expression, Rats, Wistar, Apoptosis, Sequence Homology, Amino Acid, DNA Primers, DNA, Complementary, Adaptor Proteins, Signal Transducing, Rats
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