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bioRxiv · 10.1101/377770

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

Mueller, T.·Yates, S. D.·Meador-Woodruff, J. H.
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Abstract

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.

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Mueller, T., Yates, S. D., Meador-Woodruff, J. H.. 2018-07-26. Increased α-2,8-sialyltransferase 8B (ST8SIA2) expression in schizophrenia superior temporal gyrus. https://doi.org/10.1101/377770

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