Pharmacotherapeutic Implications of the Association Between Genomic Instability at Chromosome 15q13.3 and Autism Spectrum Disorders
Abstract
Recurrent microdeletions of chromosome 15q13.3 are causally associated with autism spectrum disorders (ASDs), suggesting that haploinsufficiency of CHRNA7, the gene that codes for the α7 nicotinic acetylcholine receptor (α7 nAChR) subunit, is an etiological mechanism. Independent of these genetic data, given the location of α7 nAChRs on γ-aminobutyric acid-inhibitory neurons and their role in maintaining central inhibitory tone, a compelling pharmacological rationale exists for therapeutically targeting the α7 nAChR in persons with ASDs. Given the availability of positive allosteric modulators of nicotinic acetylcholine receptors and selective agonists for the α7 nAChR (eg, choline derived from dietary administration of cytidine 5'diphosphocholine and anabasine derivatives), it is possible to conduct "proof of concept" clinical trials, exploring the effects of α7 nAChR agonist interventional strategies on domains of psychopathology, such as attention, cognition, and memory, in persons with ASDs.
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ASD-associated genes were enriched for acetylcholinergic and serotonergic signaling.
“ASD-associated genes were enriched for acetylcholinergic and serotonergic signaling, reflecting known biology of ASD20,21.”
From A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles (2020) · cites this paper as [20]
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d-Cycloserine improves the impaired sociability of the Balb/c mouse
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Sey, N. Y. A., Hu, B., Mah, W., Fauni, H., McAfee, J. C., Rajarajan, P., Brennand, K. J., Akbarian, S., & Won, H. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0603-0 · Cited by 297 · see citing works
- Authors
- Deutsch, S. I., Urbano, M. R., Burket, J. A., Herndon, A. L., & Winebarger, E. E.
- Affiliations
- Eastern Virginia Medical School (US)
- Corresponding author
- Deutsch, Stephen I.
- ORCID
- Burket, Jessica A.
- Venue
- Clinical Neuropharmacology
- Published
- 2011-11
- Volume
- 34
- Issue
- 6
- Pages
- 203-205
- ISSN
- 0362-5664 (ISSN-L)
- OpenAlex
- W2095201394
- Cited by
- 22
- References
- 10
- Citations by year
- 2024: 1 · 2022: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 3
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, genomic instability, CHRNA7, alpha7 nicotinic acetylcholine receptor, haploinsufficiency, positive allosteric modulators, choline, GABAergic inhibition, pharmacotherapy
- MeSH terms
- Animals, Child, Child Development Disorders, Pervasive, Chromosomes, Human, Pair 15, Humans, Receptors, Nicotinic, Nicotinic Agonists, Genomic Instability, Genetic Association Studies, Haploinsufficiency, alpha7 Nicotinic Acetylcholine Receptor
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