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Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia
Abstract
Animal studies and cell culture experiments demonstrated that posttranscriptional editing of the transcript of the GluR-2 gene, resulting in substitution of an arginine for glutamine in the second transmembrane region (TM II) of the expressed protein, is associated with a reduction in Ca2+ permeability of the receptor channel. Thus, disturbances in GluR-2 RNA editing with alteration of intracellular Ca2+ homeostasis could lead to neuronal dysfunction and even neuronal degeneration. The present study determined the proportions of edited and unedited GluR-2 RNA in the prefrontal cortex of brains from patients with Alzheimer's disease, in the striatum of brains from patients with Huntington's disease, and in the same areas of brains from age-matched schizophrenics and controls, by using reverse transcriptase-polymerase chain reaction, restriction endonuclease digestion, gel electrophoresis and scintillation radiometry. In the prefrontal cortex of controls, 99.9% were edited; in the prefrontal cortex both of schizophrenics and of Alzheimer's patients approximately 1.0% of all GluR-2 RNA molecules were unedited and 99% were edited. In the striatum of controls and of schizophrenics, approximately 0.5% of GluR-2 RNA molecules were unedited and 99.5% were edited; in the striatum of Huntington's patients nearly 5.0% of GluR-2 RNA was unedited. In the prefrontal white matter of controls, approximately 7.0% of GluR-2 RNA was unedited. In the normal human prefrontal cortex and striatum,…
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“For example, in BM36, we identified well characterized A-to-I editing sites of GRIA2 (R/G and Q/R) (55, 75, 76) and GRIK2 (Q/R) (29, 77), as well as previously reported editing sites in NOVA1 (S/G) (29, 56) (Fig. 5D).”
From Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains (2025) · cites this paper as [75]
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Lismer, A., Shao, X., Dumargne, M.-C., Lafleur, C., Lambrot, R., Chan, D., Toft, G. V., Bonde, J. P., MacFarlane, A. J., Bornman, R., et al. (2024) · Environmental Health Perspectives · doi:10.1289/ehp12013 · Cited by 28
Inosine and its methyl derivatives: Occurrence, biogenesis, and function in RNA
Dutta, N., Deb, I., Sarzyńska, J., & Lahiri, A. (2022) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2022.01.001 · Cited by 23
Metadata
- Authors
- Akbarian, S., Smith, M. A., & Jones, E. G.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Jones, Edward G.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1995-11
- Volume
- 699
- Issue
- 2
- Pages
- 297-304
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2073364812
- Cited by
- 183
- References
- 61
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 3
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50mh044188-05)
- U.S. Public Health Service
- University of California, Irvine
- National Institute of Mental Health (MH44188)
- National Institute on Drug Abuse
- National Institute of Neurological Disorders and Stroke (R01NS033213, NS-33213, NS21377, R01NS021377)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- AMPA receptors, prefrontal cortex, striatum, Alzheimer's disease, Huntington's disease, schizophrenia, calcium permeability, neuronal dysfunction, neurodegeneration
- MeSH terms
- Aged, Alzheimer Disease, Autoradiography, Corpus Striatum, Humans, Huntington Disease, Middle Aged, Nerve Degeneration, RNA, Schizophrenia, Prefrontal Cortex, Receptors, AMPA
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