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Aberrant glycosylation in schizophrenia: a review of 25 years of post-mortem brain studies
- Source :
- Mol Psychiatry
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Glycosylation, the enzymatic attachment of carbohydrates to proteins and lipids, regulates nearly all cellular processes and is critical in the development and function of the nervous system. Axon pathfinding, neurite outgrowth, synaptogenesis, neurotransmission, and many other neuronal processes are regulated by glycans. Over the past 25 years, studies analyzing post-mortem brain samples have found evidence of aberrant glycosylation in individuals with schizophrenia. Proteins involved in both excitatory and inhibitory neurotransmission display altered glycans in the disease state, including AMPA and kainate receptor subunits, glutamate transporters EAAT1 and EAAT2, and the GABA(A) receptor. Polysialylated NCAM (PSA-NCAM) and perineuronal nets (PNNs), highly glycosylated molecules critical for axonal migration and synaptic stabilization, are both downregulated in multiple brain regions of individuals with schizophrenia. Additionally, enzymes spanning several pathways of glycan synthesis show differential expression in brains of individuals with schizophrenia. These changes may be due to genetic predisposition, environmental perturbations, medication use, or a combination of these factors. However, the recent association of several enzymes of glycosylation with schizophrenia by genome-wide association studies underscores the importance of glycosylation in this disease. Understanding how glycosylation is dysregulated in the brain will further our understanding of how this pathway contributes to the development and pathophysiology of schizophrenia.
- Subjects :
- 0301 basic medicine
Glycosylation
Neurite
Synaptogenesis
Kainate receptor
AMPA receptor
Neurotransmission
Biology
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Cognition
0302 clinical medicine
Humans
Glycomics
Molecular Biology
Perineuronal net
White Matter
carbohydrates (lipids)
Psychiatry and Mental health
Glucose
030104 developmental biology
Pharmaceutical Preparations
nervous system
chemistry
Schizophrenia
Neural cell adhesion molecule
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14765578 and 13594184
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Molecular Psychiatry
- Accession number :
- edsair.doi.dedup.....1902dfe334137f64b05386432d534a0d