Aberrant glycosylation in schizophrenia: a review of 25 years of post-mortem brain studies

Williams, Samuel M.; Mealer, Robert G.; Scolnick, Edward M.; Smoller, Jordan W.; Cummings, Richard D.

doi:10.1038/s41380-020-0761-1

Cited by 46 publications

(27 citation statements)

References 96 publications

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“…Patients with SLC39A8-CDG showed a similar pattern of N-glycome changes that were reversed after a year of treatment with Mn, suggesting that glycome alterations and associated phenotypes in A391T carriers may be amenable to Mn supplementation. We hypothesize that dysregulated glycosylation may be a feature of schizophrenia pathogenesis, as in addition to SLC39A8 , several glycosylation enzymes are associated with the disorder by GWAS 42 , and many studies have shown glycosylation changes in post-mortem brain of individuals with schizophrenia 43 .…”

Section: Discussionmentioning

confidence: 99%

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

Mealer

Jenkins

Chen

et al. 2020

Sci Rep

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A common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations in SLC39A8 result in undetectable serum manganese (Mn) and a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity of glycosyltransferases to Mn concentration. Here, we identified several Mn-related changes in human carriers of the common SLC39A8 missense allele. Analysis of structural brain MRI scans showed a dose-dependent change in the ratio of T2w to T1w signal in several regions. Comprehensive trace element analysis confirmed a specific reduction of only serum Mn, and plasma protein N-glycome profiling revealed reduced complexity and branching. N-glycome profiling from two individuals with SLC39A8-CDG showed similar but more severe alterations in branching that improved with Mn supplementation, suggesting that the common variant exists on a spectrum of hypofunction with potential for reversibility. Characterizing the functional impact of this variant will enhance our understanding of schizophrenia pathogenesis and identify novel therapeutic targets and biomarkers.

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Section: Discussionmentioning

confidence: 99%

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

Mealer

Jenkins

Chen

et al. 2020

Sci Rep

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“…The forebrain as a unit, and the cortex and hippocampus as specialized derived structures, centralize the processing of information related to cognitive activities and behavior. Dysregulation of brain sialylation levels has been reported in CDG, psychiatric diseases such as schizophrenia, during aging, and in neurodegenerative disorders like Alzheimer's and Parkinson's diseases (2,29,31,49,53).…”

Section: Cerebral Cortex Hippocampus and Cerebellum N-glycomesmentioning

confidence: 99%

Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis

Barboza

Solakyıldırım

Luke

et al. 2021

Molecular & Cellular Proteomics

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Aberrant glycosylation in schizophrenia was also the topic of a review of 25 years of post-mortem brain studies by Williams et al [21]. They point out the same observation noted by Mealer et al [20] that there is recent evidence for the association of several enzymes of glycosylation with schizophrenia by GWAS, which shows the importance of glycosylation in this disease.…”

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confidence: 74%

“…It is remarkable that these four outstanding papers provide an in-depth understanding of both glycobiology [20,21], white matter abnormalities [23], well as well as their interactions in schizophrenia [22]. In future issues, Molecular Psychiatry will continue to publish outstanding advances in schizophrenia research.…”

mentioning

confidence: 99%

Advances in schizophrenia research: glycobiology, white matter abnormalities, and their interactions

Licinio

Wong

2020

Mol Psychiatry

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Aberrant glycosylation in schizophrenia: a review of 25 years of post-mortem brain studies

Cited by 46 publications

References 96 publications

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis

Advances in schizophrenia research: glycobiology, white matter abnormalities, and their interactions

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