Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The blue copper protein ceruloplasmin has been of interest to psychiatrists for decades following Heilmeyer's observation of elevated serum copper levels in schizophrenic patients. Immunoturbidimetry, however, does not yield elevated serum ceruloplasmin concentrations in schizophrenia while ceruloplasmin-related oxidase activity appears to be elevated in patients with schizophrenia and reduced in patients with Alzheimer's disease. Low serum concentrations of immuno-turbidimetrically measured ceruloplasmin, and of oxidase activity, are typical of Wilson's disease, Menkes' disease, and aceruloplasminemia, three familial neurodegenerative disorders of pronounced variability, with regard to both genotype and phenotype. Especially patients with Wilson's disease may exhibit behavioural symptoms only over a long period. Heterozygous carriers of Wilson's disease and aceruloplasminaemia may have low serum ceruloplasmin concentrations; they will not develop somatic symptoms, but the significance of these carrier states, or of "hypoceruloplasminaemia", with regard to mental disorders is unknown.
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PMID:[The role of ceruloplasmin in the differential diagnosis of neuropsychiatric disorders]. 2081 66

ATP7A mutations impair copper metabolism resulting in three distinct genetic disorders in humans. These diseases are characterized by neurological phenotypes ranging from intellectual disability to neurodegeneration. Severe ATP7A loss-of-function alleles trigger Menkes disease, a copper deficiency condition where systemic and neurodegenerative phenotypes dominate clinical outcomes. The pathogenesis of these manifestations has been attributed to the hypoactivity of a limited number of copper-dependent enzymes, a hypothesis that we refer as the oligoenzymatic pathogenic hypothesis. This hypothesis, which has dominated the field for 25 years, only explains some systemic Menkes phenotypes. However, we argue that this hypothesis does not fully account for the Menkes neurodegeneration or neurodevelopmental phenotypes. Here, we propose revisions of the oligoenzymatic hypothesis that could illuminate the pathogenesis of Menkes neurodegeneration and neurodevelopmental defects through unsuspected overlap with other neurological conditions including Parkinson's, intellectual disability, and schizophrenia.
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PMID:Molecular basis of neurodegeneration and neurodevelopmental defects in Menkes disease. 2558 85

Environmental factors and susceptible genomes interact to determine the risk of neurodevelopmental disorders. Although few genes and environmental factors have been linked, the intervening cellular and molecular mechanisms connecting a disorder susceptibility gene with environmental factors remain mostly unexplored. Here we focus on the schizophrenia susceptibility gene DTNBP1 and its product dysbindin, a subunit of the BLOC-1 complex, and describe a neuronal pathway modulating copper metabolism via ATP7A. Mutations in ATP7A result in Menkes disease, a disorder of copper metabolism. Dysbindin/BLOC-1 and ATP7A genetically and biochemically interact. Furthermore, disruption of this pathway causes alteration in the transcriptional profile of copper-regulatory and dependent factors in the hippocampus of dysbindin/BLOC-1-null mice. Dysbindin/BLOC-1 loss-of-function alleles do not affect cell and tissue copper content, yet they alter the susceptibility to toxic copper challenges in both mammalian cells and Drosophila. Our results demonstrate that perturbations downstream of the schizophrenia susceptibility gene DTNBP1 confer susceptibility to copper, a metal that in excess is a neurotoxin and whose depletion constitutes a micronutrient deficiency.
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PMID:Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. 2619 16