Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal development of the nervous system relies on the spatially and temporally well-controlled differentiation of neurons and glia. Here, we discuss the intra- and extracellular molecular mechanisms that underlie the sequential genesis of neurons and glia, emphasizing recent studies describing the role of a signaling molecule, the tyrosine phosphatase SHP2, in normal brain development. Activation of SHP2 simultaneously enhances downstream activation of the MEK-ERK pathway, which subsequently promotes neurogenesis, while inhibiting the JAK-STAT pathway, which is critical for astroglial differentiation. Mutations in SHP2 that increase its tyrosine phosphatase activity cause a mental retardation-related disorder, Noonan syndrome. An imbalance in neurogenesis versus gliogenesis due to SHP2 mutations may contribute to Noonan syndrome.
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PMID:Neurons or glia? Can SHP2 know it all? 1797 66

The present study aims to identify patterns for use of medication given pro re nata (PRN or "on an as needed [preordered] basis") or statim (STAT [a new order] or "at once, immediately") and their efficacy in controlling aggressive behavior in the mental health (MH) services environment. PRN and STAT medication data were combined and referred to as PRN throughout this article, as the data were not collected in a manner required to differentiate between PRN and STAT medication administration. Analyzed data were extracted from the clinical records of a sample of children and youth admitted for the first time to a tertiary MH center. MH Program patients (characterized by at least one Axis I psychiatric diagnosis [Axis I group]) were compared to Dual Diagnosis Program patients (characterized by an Axis I diagnosis in addition to an Axis II diagnosis of mental retardation [Axis II group]). Age, gender, Program (Axis I or II group), and the length of stay for treatment produced significant differences in the use of PRNs between the two groups. Further, the study investigated the precipitating factors leading to use of PRNs, in conjunction with the level of supervision and the de-escalation techniques used to avoid the use of PRNs. Axis I patients were more likely to endanger others, whereas Axis II patients were more likely to endanger themselves. Both groups of patients demonstrated a need for an increased level of supervision prior to the crisis. Olanzapine, chlorpromazine, and lorazepam were effective in calming patients and preventing further aggressive outbursts.
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PMID:The use of Pro Re Nata or Statim medications for behavioral control: a summary of experience at a tertiary care children's mental health center. 2128 18

Appropriate expression of growth-regulatory genes is essential to ensure normal animal development and to prevent diseases like cancer. Gene regulation at the levels of transcription and translational initiation mediated by the Hippo and Insulin signaling pathways and by the TORC1 complex, respectively, has been well documented. Whether translational control mediated by RNA-binding proteins contributes to the regulation of cellular growth is less clear. Here, we identify Lingerer (Lig), an UBA domain-containing protein, as growth suppressor that associates with the RNA-binding proteins Fragile X mental retardation protein 1 (FMR1) and Caprin (Capr) and directly interacts with and regulates the RNA-binding protein Rasputin (Rin) in Drosophila melanogaster. lig mutant organs overgrow due to increased proliferation, and a reporter for the JAK/STAT signaling pathway is upregulated in a lig mutant situation. rin, Capr or FMR1 in combination as double mutants, but not the respective single mutants, display lig like phenotypes, implicating a redundant function of Rin, Capr and FMR1 in growth control in epithelial tissues. Thus, Lig regulates cell proliferation during development in concert with Rin, Capr and FMR1.
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PMID:The RNA-binding proteins FMR1, rasputin and caprin act together with the UBA protein lingerer to restrict tissue growth in Drosophila melanogaster. 2387 12

Down syndrome (DS) is caused by trisomy for human chromosome 21. Individuals with DS commonly exhibit mental retardation, which is associated with abnormal brain development. In the neocortex of the DS brain, the density of neurons is markedly reduced, whereas that of astrocytes is increased. Similar to abnormalities seen in DS brains, mouse models of DS show deficits in brain development, and neural progenitor cells that give rise to neurons and glia show dysregulation in their differentiation. These suggest that the dysregulation of progenitor fate choices contributes to alterations in the numbers of neurons and astrocytes in the DS brain. Nevertheless, the molecular basis underlying these defects remains largely unknown. We showed that the overexpression of two human chromosome 21 genes, DYRK1A and DSCR1, contributes to suppressed neuronal differentiation of progenitors in the Ts1Cje mouse model of DS. In addition, the effect of DYRK1A and DSCR1 overexpression on neuronal differentiation is mediated by excessive attenuation of the transcription factor NFATc. Additionally, we demonstrated that an increased dosage of DYRK1A contributes to elevated potential of Ts1Cje progenitors to differentiate into astrocytes and enhanced astrogliogenesis in the Ts1Cje neocortex. Further, we linked the increased dosage of DYRK1A to dysregulation of STAT, a transcription factor critical for astrogliogenesis. Together, our studies identify critical pathways responsible for the proper differentiation of neural progenitors into neurons and astrocytes, with direct implications for the anomalies in brain development observed in DS.
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PMID:Molecular Mechanism Underlying Abnormal Differentiation of Neural Progenitor Cells in the Developing Down Syndrome Brain. 2867 89