DISC1 a key molecular lead in psychiatry and neurodevelopment: No-More Disrupted-in-Schizophrenia 1

Niwa, Minae; Cash-Padgett, Tyler; Kubo, Keishi; Saito, Atsushi; Ishii, Kazuhiro; Sumitomo, Akiko; Taniguchi, Yu; Ishizuka, Koko; Jaaro-Peled, Hanna; Tomoda, Toshifumi; Nakajima, Kazunori; Sawa, Akira; Kamiya, Atsushi

doi:10.1038/mp.2016.154

Cited by 63 publications

(55 citation statements)

References 15 publications

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“…The activity of PDE4 is physiologically regulated at various levels, including intracellular localization, protein interaction, and posttranslational modifications (14,19). One of the critical direct interactors with PDE4 is the scaffold protein DISC1 (17,(20)(21)(22)(23). Physiological roles for DISC1 in biological pathways in brain development and neurosignaling have been intensively studied for the past decade in various animal models (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Tanaka

Ishizuka

Nekooki

et al. 2017

Journal of the Neurological Sciences

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Section: Introductionmentioning

confidence: 99%

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Tanaka

Ishizuka

Nekooki

et al. 2017

Journal of the Neurological Sciences

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“…Several genetic factors associated with the risk of development of neuropsychiatric disorders have been reported to have an influence on neuronal migration during development. We previously reported that developmental perturbations of disrupted‐in‐schizophrenia 1 ( DISC1 ), known as a susceptibility factor for mental disorders, resulted in neuronal migration delays in the neocortex and hippocampus . We also showed that neuronal migration delays during development result in abnormal distributions of neurons in mature brains, including increase in the number/densities of ectopic neurons in the WM, suggesting that the increased densities/numbers of the WM neurons in the brains of patients with neuropsychiatric disorders could be an outcome of migration delays during brain development.…”

Section: What Is the Cause(s) Of The Increased Densities/number Of Wmmentioning

confidence: 99%

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

Kubo

2020

Psychiatry Clin Neurosci

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While neurons of the human cerebral cortex are mainly distributed in the gray matter, the white matter (WM) also contains some excitatory and inhibitory neurons, so‐called WM neurons. Studies on the cytoarchitectural alterations in the brains of patients with neuropsychiatric disorders have repeatedly reported increased densities of the WM neurons in a proportion of patients with schizophrenia and autism spectrum disorder. Although some studies have demonstrated increased densities of superficial WM neurons, others have demonstrated increased densities of deep WM neurons and increased WM neuron densities can be considered as one of the cross‐disease features of neuropsychiatric disorders. Nevertheless, what actually causes the increase in the densities of the WM neurons still remains under debate, and several hypothetical mechanisms have been proposed. The WM neurons in normal brains are considered as remnants of the subplate neurons, which represent a transient cytoarchitectural zone present during development of the mammalian neocortex; it has been suggested that increased densities of the WM neurons could result from inappropriate apoptosis of the subplate neurons in the brains of patients with neuropsychiatric disorders. On the other hand, recent experimental studies have demonstrated that genetic and environmental factors that enhance the risk of development of neuropsychiatric disorders could cause altered distribution of neurons in the WM. To understand the pathophysiology underlying the increased densities of the WM neurons, it is important to investigate the cellular characteristics of the WM neurons in the brains of both normal subjects and patients with neuropsychiatric disorders.

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“…While the remaining genes-RAD51B, NCALD, and DISC1-are rarely reported in AD, they share a common trait: they have been associated with the amyloid precursor gene APP [98,99]. Furthermore, it has been suggested that DISC1 plays a much broader role than "disrupted in schizophrenia" for DISC1 [100]. DISC1 has been reported in lateonset AD [101] and has also been associated with both APP and Aβ production [102].…”

Section: Rbfox1 and Gpc6mentioning

confidence: 99%

Multivariate genotypic analyses that identify specific genotypes to characterize disease and control groups in ADNI

Beaton

Rieck

Alhazmi³

et al. 2017

Preprint

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INTRODUCTIONGenetic contributions to Alzheimer’s Disease (AD) are likely polygenic and not necessarily explained by uniformly applied linear and additive effects. In order to better understand the genetics of AD, we require statistical techniques to address both polygenic and possible non-additive effects.METHODSWe used partial least squares-correspondence analysis (PLS-CA)—a method designed to detect multivariate genotypic effects. We used ADNI-1 (N = 756) as a discovery sample with two forms of PLS-CA: diagnosis-based and ApoE-based. We used ADNI-2 (N= 791) as a validation sample with a diagnosis-based PLS-CA.RESULTSWith PLS-CA we identified some expected genotypic effects (e.g., APOE/TOMM40, and APP) and a number of new effects that include, for examples, risk-associated genotypes in RBFOX1 and GPC6 and control-associated genotypes in PTPN14 and CPNE5.DISCUSSIONThrough the use of PLS-CA, we were able to detect complex (multivariate, genotypic) genetic contributions to AD, which included many non-additive and non-linear risk and possibly protective effects.

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DISC1 a key molecular lead in psychiatry and neurodevelopment: No-More Disrupted-in-Schizophrenia 1

Cited by 63 publications

References 15 publications

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

Multivariate genotypic analyses that identify specific genotypes to characterize disease and control groups in ADNI

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