L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development
ABSTRACTRecent human genetic studies have linked a variety of genetic variants in the CACNA1C and CACNA1D genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Cav1.2 and Ca...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Channels |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19336950.2023.2176984 |
| _version_ | 1797449019804352512 |
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| author | Madelyn R. Baker Andrew S. Lee Anjali M. Rajadhyaksha |
| author_facet | Madelyn R. Baker Andrew S. Lee Anjali M. Rajadhyaksha |
| author_sort | Madelyn R. Baker |
| collection | DOAJ |
| description | ABSTRACTRecent human genetic studies have linked a variety of genetic variants in the CACNA1C and CACNA1D genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Cav1.2 and Cav1.3 L-type calcium channels (LTCCs), encoded by CACNA1C and CACNA1D, respectively, play a key role in various neuronal processes that are essential for normal brain development, connectivity, and experience-dependent plasticity. Of the multiple genetic aberrations reported, genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) in CACNA1C and CACNA1D that are present within introns, in accordance with the growing body of literature establishing that large numbers of SNPs associated with complex diseases, including neuropsychiatric disorders, are present within non-coding regions. How these intronic SNPs affect gene expression has remained a question. Here, we review recent studies that are beginning to shed light on how neuropsychiatric-linked non-coding genetic variants can impact gene expression via regulation at the genomic and chromatin levels. We additionally review recent studies that are uncovering how altered calcium signaling through LTCCs impact some of the neuronal developmental processes, such as neurogenesis, neuron migration, and neuron differentiation. Together, the described changes in genomic regulation and disruptions in neurodevelopment provide possible mechanisms by which genetic variants of LTCC genes contribute to neuropsychiatric and neurodevelopmental disorders. |
| first_indexed | 2024-03-09T14:18:50Z |
| format | Article |
| id | doaj.art-8bc61feed9044c26881d1ca1bee22015 |
| institution | Directory Open Access Journal |
| issn | 1933-6950 1933-6969 |
| language | English |
| last_indexed | 2024-03-09T14:18:50Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Channels |
| spelling | doaj.art-8bc61feed9044c26881d1ca1bee220152023-11-28T18:09:44ZengTaylor & Francis GroupChannels1933-69501933-69692023-12-0117110.1080/19336950.2023.2176984L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain developmentMadelyn R. Baker0Andrew S. Lee1Anjali M. Rajadhyaksha2Neuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, USANeuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, USANeuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, USAABSTRACTRecent human genetic studies have linked a variety of genetic variants in the CACNA1C and CACNA1D genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Cav1.2 and Cav1.3 L-type calcium channels (LTCCs), encoded by CACNA1C and CACNA1D, respectively, play a key role in various neuronal processes that are essential for normal brain development, connectivity, and experience-dependent plasticity. Of the multiple genetic aberrations reported, genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) in CACNA1C and CACNA1D that are present within introns, in accordance with the growing body of literature establishing that large numbers of SNPs associated with complex diseases, including neuropsychiatric disorders, are present within non-coding regions. How these intronic SNPs affect gene expression has remained a question. Here, we review recent studies that are beginning to shed light on how neuropsychiatric-linked non-coding genetic variants can impact gene expression via regulation at the genomic and chromatin levels. We additionally review recent studies that are uncovering how altered calcium signaling through LTCCs impact some of the neuronal developmental processes, such as neurogenesis, neuron migration, and neuron differentiation. Together, the described changes in genomic regulation and disruptions in neurodevelopment provide possible mechanisms by which genetic variants of LTCC genes contribute to neuropsychiatric and neurodevelopmental disorders.https://www.tandfonline.com/doi/10.1080/19336950.2023.2176984CACNA1CCACNA1DCav1.2Cav1.3neuropsychiatric |
| spellingShingle | Madelyn R. Baker Andrew S. Lee Anjali M. Rajadhyaksha L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development Channels CACNA1C CACNA1D Cav1.2 Cav1.3 neuropsychiatric |
| title | L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development |
| title_full | L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development |
| title_fullStr | L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development |
| title_full_unstemmed | L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development |
| title_short | L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development |
| title_sort | l type calcium channels and neuropsychiatric diseases insights into genetic risk variant associated genomic regulation and impact on brain development |
| topic | CACNA1C CACNA1D Cav1.2 Cav1.3 neuropsychiatric |
| url | https://www.tandfonline.com/doi/10.1080/19336950.2023.2176984 |
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