Ask about this productRelated genes to: DISC1 antibody
- Gene:
- DISC1 NIH gene
- Name:
- DISC1 scaffold protein
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q42.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-01-20
- Date modifiied:
- 2018-03-01
- Gene:
- DISC2 NIH gene
- Name:
- disrupted in schizophrenia 2
- Previous symbol:
- -
- Synonyms:
- DISC1-AS1, DISC1OS, NCRNA00015
- Chromosome:
- 1q42.1
- Locus Type:
- RNA, long non-coding
- Date approved:
- 2000-01-20
- Date modifiied:
- 2018-05-16
Related products to: DISC1 antibody
Related articles to: DISC1 antibody
- Stem cell-derived extracellular vesicles (EVs) show promise as a therapeutic approach for neurodegenerative diseases, particularly Alzheimer's Disease (AD), where traditional regenerative interventions have achieved limited success. Our previous research demonstrated the neuroprotective benefits of human neural stem cell (hNSC)-derived EVs in 2- and 6-month-old AD mice (5xFAD) that exibited improved cognitive function and reduced AD-related neuropathology. This study aimed to compare the neuroprotective efficacy of EVs derived from two human cell lines: hNSCs from H9 embryonic stem cells and human iPSC-derived microglia (iMGLs). Additionally, we investigated the efficacy of an expanded EV treatment paradigm at subsequently longer time points. Three-month-old 5xFAD mice received weekly retro-orbital vein injections of either hNSC- or iMGL-derived EVs for 4 weeks. Cognitive function testing revealed comparable cognitive improvements in both EV treatment groups compared to vehicle-injected AD mice. Both iMGL- and hNSC-derived EVs significantly reduced amyloid beta plaques, astrogliosis, and microglial activation, while restoring synaptophysin and postsynaptic density protein PSD-95 to control levels in AD brains. Gene expression analysis revealed significantly reduced neuroinflammation and elevated neuroprotective signatures following both EV treatments. MicroRNA analysis of the EV-derived cargo revealed unique and shared miRNA signatures associated with differentially expressed genes in both cell lines. These findings demonstrate the feasibility and neuroprotective benefits of recurrent systemic injections of EVs derived from human NSCs and differentiated human microglia lines in alleviating cognitive dysfunction and neuropathology in Alzheimer's disease. - Source: PubMed
Krattli Robert PMarkarian MinehMadan ShreyaSwami DevyaniMcQuade AmandaBaulch Janet EBlurton-Jones MatthewAcharya Munjal M - Bipolar disorder (BD) is a mental disorder that is often misdiagnosed with ineffective treatment. It has strong genetic component but unknown pathophysiology. Long non-coding RNAs (lncRNAs) have been recently recognized as one of the important genetic factors and are considered as one of the regulatory mechanisms of nervous system. Given that lncRNAs may be diagnostic biomarkers for BD, we aimed to quantify the levels of DISC1 and DISC2 lncRNA transcripts. The levels of DISC1 and DISC2 lncRNA were tested in peripheral blood mononuclear cells (PBMCs) of 50 BD and 50 controls by real-time PCR. In addition, we performed ROC curve analysis as well as correlation analysis between the gene expression and some clinical features of BD cases. Computational analysis of miRNAs binding sites and CpG Islands on DISC1 and DISC2 lncRNA was performed as well. Significant down-regulation of DISC1 and up-regulation of DISC2 were observed in BD cases compared with controls. The areas under the ROC curve (AUC) for DISC1 and DISC2 lncRNA were 0.76 and 0.68 respectively. There was no significant correlation between the levels of mRNA expression in PBMCs of BD patients and clinical features. These data demonstrated that DISC1 and DISC2 lncRNA expression was potentially associated with an increased risk of bipolar disorder and might involve several molecular mechanisms. Our results revealed that the transcript levels of DISC1 and DISC2 lncRNA could be considered as a good putative biomarker for individuals with bipolar disorder. - Source: PubMed
Publication date: 2018/12/29
Naghavi-Gargari BaharZahirodin AlirezaGhaderian Sayyed Mohammad HosseinShirvani-Farsani Zeinab - Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes. - Source: PubMed
Publication date: 2018/06/07
Ryan Niamh MLihm JayonKramer MelissaMcCarthy ShaneMorris Stewart WArnau-Soler AleixDavies GailDuff BarbaraGhiban ElenaHayward CarolineDeary Ian JBlackwood Douglas H RLawrie Stephen MMcIntosh Andrew MEvans Kathryn LPorteous David JMcCombie W RichardThomson Pippa A - - Source: PubMed
Ren JunZhao TianHan Yu-Ying - In a large Scottish pedigree, a balanced translocation t (1;11)(q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family with schizophrenia, but subsequently found in two controls. Herein, we test one hypothesis utilizing a large scale case-control mutation analysis: uncommon DISC1 variants are associated with high risk for bipolar spectrum disorder. We have analyzed the regions of likely functional significance in the DISC1 gene in 504 patients with bipolar spectrum disorder and 576 ethnically similar controls. Five patients were heterozygous for ultra-rare protein structural variants not found in the 576 controls (p=0.02, one-sided Fisher's exact test) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. In our sample, ultra-rare (private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. These data are consistent with: (i) the high frequency of depression in the large Scottish family with a translocation disrupting DISC1; (ii) linkage disequilibrium analysis demonstrating haplotypes associated with relatively small increases in risk for bipolar disorder (<3-fold odds ratio). The data illustrate how low/moderate risk haplotypes that might be found by the HapMap project can be followed up by resequencing to identify protein structural variants with high risk, low frequency and of potential clinical utility. - Source: PubMed
Publication date: 2010/09/17
Song WenjiaLi WenyanNoltner KatieYan JinGreen ElaineGrozeva DetelinaJones Ian RCraddock NickLongmate JeffFeng JinongSommer Steve S