Mental disorders and an acidic glycan-from the perspective of polysialic acid (PSA/polySia) and the synthesizing enzyme, ST8SIA2

Abstract

Mental disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder, are challenging to manage, worldwide. Understanding the molecular mechanisms underlying these disorders is essential and required. Studies investigating such molecular mechanisms are well performed and important findings are accumulating apace. Based on the fact that these disorders are due in part to the accumulation of genetic and environmental risk factors, consideration of multi-molecular and/or multi-system dependent phenomena might be important. Acidic glycans are an attractive family of molecules for understanding these disorders, because impairment of the fine-tuned glycan system affects a large number of molecules that are deeply involved in normal brain function. One of the candidates of this important family of glycan epitopes in the brain is polysialic acid (PSA/polySia). PSA is a well-known molecule because of its role as an oncodevelopmental antigen and is also widely used as a marker of adult neurogenesis. Recently, several reports have suggested that PSA and PSA-related genes are associated with multiple mental disorders. The relationships among PSA, PSA-related genes, and mental disorders are reviewed here.

Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain

“…The relationship between polySia and/or the ST8SIA2 and mental disorders was recently reported 21 . In the brains of patients with SCZ, polySia expression is decreased in the PFC 16 and HIP 15 .…”

“…In the brains of patients with SCZ, polySia expression is decreased in the PFC 16 and HIP 15 . Interestingly, several significant SNPs of the ST8SIA2 that express an enzyme responsible for polySia synthesis are reportedly related to SCZ and BD 21 . Precise biochemical examination of the significant SNPs revealed changes in polySia expression, structure and functions 21 .…”

“…Interestingly, several significant SNPs of the ST8SIA2 that express an enzyme responsible for polySia synthesis are reportedly related to SCZ and BD 21 . Precise biochemical examination of the significant SNPs revealed changes in polySia expression, structure and functions 21 . In addition, St8sia2 -KO mice have been reported to be a model of SCZ 27 .…”

“…The polysialyltransferase, ST8 alpha- N -acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) is responsible for polySia synthesis 20 . A relationship between mental disorders and SNPs of ST8SIA2 has been demonstrated 21 . In addition, biochemical analyses revealed the involvement of some of these SNPs in the structural and functional impairment of polySia 21,22 .…”

“…A relationship between mental disorders and SNPs of ST8SIA2 has been demonstrated 21 . In addition, biochemical analyses revealed the involvement of some of these SNPs in the structural and functional impairment of polySia 21,22 . For example, the rs545681995 SNP leads to a single amino acid change and the resulting mutated ST8SIA2 led to reduced polySia synthetic activity and impaired quantity and length of polySia 23,24 .…”