Relationship between ST8SIA2, polysialic acid and its binding molecules, and psychiatric disorders

• Published in: Biochimica et biophysica acta Vol. 1860; no. 8; pp. 1739 - 1752
• Main Authors: Sato, Chihiro, Hane, Masaya, Kitajima, Ken
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2016
• Subjects: Autism; Bipolar disorder; brain; Brain - metabolism; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; dopamine; Dopamine - genetics; Dopamine - metabolism; genes; genetic variation; Genome-Wide Association Study; Humans; medicine; memory; Mental Disorders - genetics; Mental Disorders - metabolism; Neural cell adhesion molecule; patients; Polymorphism, Single Nucleotide; polysaccharides; Polysialic acid; Polysialyltransferase; Psychiatric disorder; Schizophrenia; Sialic Acids - genetics; Sialic Acids - metabolism; Sialyltransferases - genetics; Sialyltransferases - metabolism; single nucleotide polymorphism; SNPs; social behavior; vertebrates; Polysialyltransferase; BD; Neural cell adhesion molecule; BDNF; ST8SIA2; Polysialic acid; SZ; SGZ; Schizophrenia; Bipolar disorder; FGF2; HIP; Psychiatric disorder; polySia; Autism; ASD; OB; SNP; SVZ; SNPs; NACM; AMG; DA; PSA
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.04.015

Polysialic acid (polySia, PSA) is a unique and functionally important glycan, particularly in vertebrate brains. It is involved in higher brain functions such as learning, memory, and social behaviors. Recently, an association between several genetic variations and single nucleotide polymorphisms (SNPs) of ST8SIA2/STX, one of two polysialyltransferase genes in vertebrates, and psychiatric disorders, such as schizophrenia (SZ), bipolar disorder (BD), and autism spectrum disorder (ASD), was reported based on candidate gene approaches and genome-wide studies among normal and mental disorder patients. It is of critical importance to determine if the reported mutations and SNPs in ST8SIA2 lead to impairments of the structure and function of polySia, which is the final product of ST8SIA2. To date, however, only a few such forward-directed studies have been conducted. In addition, the molecular mechanisms underlying polySia-involved brain functions remain unknown, although polySia was shown to have an anti-adhesive effect. In this report, we review the relationships between psychiatric disorders and polySia and/or ST8SIA2, and describe a new function of polySia as a regulator of neurologically active molecules, such as brain-derived neurotrophic factor (BDNF) and dopamine, which are deeply involved in psychiatric disorders. This article is part of a Special Issue entitled “Glycans in personalised medicine” Guest Editor: Professor Gordan Lauc. •An association between genetic variations of ST8SIA2 gene and psychiatric disorders is suggested.•The forward-directed experiments indicate that SNP or genetic variations in ST8SIA2 gene alter and impair the gene and protein expression of ST8SIA2, and subsequently structure and function of polySia.•An impairment of the structure and function of polySia might be an important aspect to understand the psychiatric disorders.