Biology subjects

Meador-Woodruff, J. H.

Publications and source records attributed to Meador-Woodruff, J. H..

2 recordsLinked to original sources

bioRxiv2018

Increased α-2,8-sialyltransferase 8B (ST8SIA2) expression in schizophrenia superior temporal gyrus

Reduced polysialylation of neural cell adhesion molecule (NCAM) in schizophrenia has been suggested to contribute to abnormal neuroplasticity and neurodevelopmental features of this illness. The posttranslational addition of sialic acid is mediated by sialyltransferases, and polysialylation (the addition of [≥] 8 -2,8-linked sialic acid residues) is catalyzed by three enzymes: ST8SIA2 (also called STX), ST8SIA4 (also called PST), and/or ST8SIA3. ST8SIA2 and ST8SIA4 are the primary mediators of NCAM polysialylation. The gene encoding ST8SIA2 maps to schizophrenia risk locus 15q26, and single nucleotide polymorphisms (SNPs) and SNP haplotypes of the ST8SIA2 gene have been associated with schizophrenia in multiple populations. The current study in elderly schizophrenia (N = 16) and comparison (N = 14) subjects measured the protein expression of NCAM, polysialylated-NCAM (PSANCAM), and three poly--2,8-sialyltransferases (ST8SIA2, ST8SIA3, and ST8SIA4) in postmortem superior temporal gyrus. Although expression of NCAM, PSA-NCAM, ST8SIA3, and ST8SIA4 were not different in schizophrenia, increased protein levels of ST8SIA2 were identified. It has been reported that ST8SIA2 mutations associated with increased schizophrenia risk impair PSA-NCAM synthesis, suggesting that increased protein expression of ST8SIA2 may represent a compensatory mechanism in the face of impaired enzyme function. This interpretation is further supported by our finding that the relationship between ST8SIA2 enzyme expression and PSA-NCAM levels are different between schizophrenia and comparison subjects. Together these findings suggest a possible neurodevelopmentally-regulated mechanism which could contribute to abnormal synaptic plasticity evident in schizophrenia.

neuroscience↗

bioRxiv2018

Glycosylation enzyme mRNA expression in dorsolateral prefrontal cortex of elderly patients with schizophrenia: Evidence for dysregulation of multiple glycosylation pathways

Altered protein post-translational modifications such as glycosylation have become a target of investigation in the pathophysiology of schizophrenia. Disrupted glycosylation associated processes including atypical sphingolipid metabolism, reduced polysialylation of cell adhesion molecules, abnormal proteoglycan expression, and irregular glycan synthesis and branching have also been reported in this disorder. These pathways are regulated by the expression of glycosidases and glycosyltransferases, classes of enzymes which comprise approximately 2% of the genome. Many glycosylation enzymes can participate in multiple glycosylation pathways and dysregulation of enzyme expression could represent a common mechanism leading to a variety of glycan processing deficits in schizophrenia. In matched pairs of elderly schizophrenia and comparison subject (N = 12 pairs) dorsolateral prefrontal cortex, we measured mRNA levels of 84 key glycosylation enzymes by qPCR array. We found dysregulated transcript expression of 36 glycosylation enzymes from 12 functional categories. All of the abnormally expressed enzymes demonstrated increased transcript expression in schizophrenia, and many altered enzymes are known to modify substrates that have been previously implicated in the pathophysiology this illness. These findings suggest that abnormal glycosylation enzyme expression in schizophrenia may contribute to dysregulation of multiple glycosylation pathways, and disruptions of these central cell signaling processes may underlie a variety of deficits in schizophrenia.

neuroscience↗