Abnormal N-acetylglucosaminyltransferase expression in prefrontal cortex in schizophrenia

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Posttranslational modification, glycosylation, is altered in schizophrenia, affecting protein function and trafficking.
• Previous studies indicate abnormal glycan biosynthesis and altered glycosyltransferase expression in schizophrenia.
• N-acetylglucosaminyltransferases (GlcNAcTs) are crucial for protein trafficking and cellular function.

Purpose of the Study:

• To investigate the protein expression of nine distinct GlcNAcTs in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia.
• To determine if GlcNAcTs are abnormally expressed in schizophrenia, potentially contributing to disease mechanisms.

Main Methods:

• Western blot analysis was used to measure the protein expression of nine GlcNAcTs.
• Postmortem DLPFC samples from elderly patients with schizophrenia and matched comparison subjects were analyzed.
• Protein expression levels were compared between the schizophrenia and control groups.

Main Results:

• Decreased protein expression of UDP-GlcNAc:BetaGal Beta-1,3 GlcNAcT 8 (B3GNT8) was observed in schizophrenia.
• Reduced protein expression of mannosyl (alpha-1,3-)-glycoprotein beta-1,4 GlcNAcT (MGAT4A) was found in schizophrenia.
• These findings indicate dysregulation of specific GlcNAcTs in schizophrenia.

Conclusions:

• Glycosylation is dysregulated in schizophrenia, supporting previous findings.
• Altered expression of GlcNAcTs may contribute to schizophrenia pathophysiology through impaired protein function, trafficking, and targeting.
• These results highlight a potential molecular mechanism underlying schizophrenia.