A Review of Disrupted-in-Schizophrenia-1 (disc1): Neurodevelopment, Cognition, and Mental Conditions
Abstract
Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.
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DISC1 is important for development of the PFC, but loss of function of DISC1 likely leads to increased cAMP-HCN signalling in spines and thus to PFC network disconnection.
“DISC1 is important for the development of the PFC131, but it is also likely that loss of function of DISC1 leads to increased cAMP–HCN signalling in spines132 and thus to PFC network disconnection.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [131]
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- Authors
- Ishizuka, K., Paek, M., Kamiya, A., & Sawa, A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sawa, Akira
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 59
- Issue
- 12
- Pages
- 1189-1197
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2042393535
- Cited by
- 190
- References
- 4
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 10 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 5 · 2012: 8
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH069853, MH069853)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- DISC1, disrupted-in-schizophrenia 1, schizophrenia, bipolar disorder, candidate genes, post-translational modification, cAMP signaling, haploinsufficiency, dominant negative mutation, animal models of schizophrenia, brain development, cognition
- MeSH terms
- Animals, Bipolar Disorder, Brain, Cognition, Disease Models, Animal, Female, Humans, Male, Nerve Tissue Proteins, Schizophrenia, Mice
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