研究者詳細 - 佐藤　ちひろ

論文 - 佐藤　ちひろ

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Polysialylation in a DISC1 Mutant Mouse. 国際誌 Open Access

Takahashi Y, Abe C, Hane M, Wu D, Kitajima K, Sato C

International journal of molecular sciences 23 巻 ( 9 ) 頁： 5207 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

Schizophrenia is a serious psychiatric disorder that affects the social life of patients. Psychiatric disorders are caused by a complex combination of genetic (G) and environmental (E) factors. Polysialylation represents a unique posttranslational modification of a protein, and such changes in neural cell adhesion molecules (NCAMs) have been reported in postmortem brains from patients with psychiatric disorders. To understand the G × E effect on polysialylated NCAM expression, in this study, we performed precise measurements of polySia and NCAM using a disrupted-in-schizophrenia 1 (DISC1)-mutant mouse (G), a mouse model of schizophrenia, under acute stress conditions (E). This is the first study to reveal a lower number and smaller length of polySia in the suprachiasmatic nucleus of DISC1 mutants relative to those in wild-type (WT) mice. In addition, an analysis of polySia and NCAM responses to acute stress in five brain regions (olfactory bulb, prefrontal cortex, suprachiasmatic nucleus, amygdala, and hippocampus) revealed that the pattern of changes in these responses in WT mice and DISC1 mutants differed by region. These differences could indicate the vulnerability of DISC1 mutants to stress.

DOI： 10.3390/ijms23095207

Role of Polysialic Acid in Schizophrenia

Sato C., Hane M., Kitajima K.

Comprehensive Glycoscience Second Edition 頁： 276 - 286 2021年6月

Polysialylation and disease. 査読有り国際誌 Open Access

Sato C, Kitajima K

Molecular aspects of medicine 79 巻頁： 100892 - 100892 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Molecular Aspects of Medicine

Polysialic acid (polySia, PSA) is a unique constituent of the glycocalyx on the surface of bacterial and vertebrate cells. In vertebrates, its biosynthesis is highly regulated, not only in quantity and quality, but also in time and location, which allows polySia to be involved in various important biological phenomena. Therefore, impairments in the expression and structure of polySia sometimes relate to diseases, such as schizophrenia, bipolar disorder, and cancer. Some bacteria express polySia as a tool for protecting themselves from the host immune system during invasion. PolySia is proven to be a biosafe material; polySia, as well as polySia-recognizing molecules, are key therapeutic agents. This review first comprehensive outlines the occurrence, features, biosynthesis, and functions of polySia and subsequently focuses on the related diseases.

DOI： 10.1016/j.mam.2020.100892

Evolutionary conservation of human ketodeoxynonulosonic acid production is independent of sialoglycan biosynthesis. 査読有り国際共著国際誌 Open Access

Kawanishi K, Saha S, Diaz S, Vaill M, Sasmal A, Siddiqui SS, Choudhury B, Sharma K, Chen X, Schoenhofen IC, Sato C, Kitajima K, Freeze HH, Münster-Kühnel A, Varki A

The Journal of clinical investigation 131 巻 ( 5 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Investigation

Human metabolic incorporation of nonhuman sialic acid (Sia) N-glycolylneuraminic acid into endogenous glycans generates inflammation via preexisting antibodies, which likely contributes to red meat-induced atherosclerosis acceleration. Exploring whether this mechanism affects atherosclerosis in end-stage renal disease (ESRD), we instead found serum accumulation of 2-keto-3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (Kdn), a Sia prominently expressed in cold-blooded vertebrates. In patients with ESRD, levels of the Kdn precursor mannose also increased, but within a normal range. Mannose ingestion by healthy volunteers raised the levels of urinary mannose and Kdn. Kdn production pathways remained conserved in mammals but were diminished by an M42T substitution in a key biosynthetic enzyme, N-acetylneuraminate synthase. Remarkably, reversion to the ancestral methionine then occurred independently in 2 lineages, including humans. However, mammalian glycan databases contain no Kdn-glycans. We hypothesize that the potential toxicity of excess mannose in mammals is partly buffered by conversion to free Kdn. Thus, mammals probably conserve Kdn biosynthesis and modulate it in a lineage-specific manner, not for glycosylation, but to control physiological mannose intermediates and metabolites. However, human cells can be forced to express Kdn-glycans via genetic mutations enhancing Kdn utilization, or by transfection with fish enzymes producing cytidine monophosphate-Kdn (CMP-Kdn). Antibodies against Kdn-glycans occur in pooled human immunoglobulins. Pathological conditions that elevate Kdn levels could therefore result in antibody-mediated inflammatory pathologies.

DOI： 10.1172/JCI137681

Exploring the Impact of Ketodeoxynonulosonic Acid in Host-Pathogen Interactions Using Uptake and Surface Display by Nontypeable Haemophilus influenzae. 国際共著国際誌 Open Access

Saha S, Coady A, Sasmal A, Kawanishi K, Choudhury B, Yu H, Sorensen RU, Inostroza J, Schoenhofen IC, Chen X, Münster-Kühnel A, Sato C, Kitajima K, Ram S, Nizet V, Varki A

mBio 12 巻 ( 1 ) 頁： 1 - 24 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Mbio

Surface expression of the common vertebrate sialic acid (Sia) N-acetyl-neuraminic acid (Neu5Ac) by commensal and pathogenic microbes appears structurally to represent “molecular mimicry” of host sialoglycans, facilitating multiple mechanisms of host immune evasion. In contrast, ketodeoxynonulosonic acid (Kdn) is a more ancestral Sia also present in prokaryotic glycoconjugates that are structurally quite dis-tinct from vertebrate sialoglycans. We detected human antibodies against Kdn-termi-nated glycans, and sialoglycan microarray studies found these anti-Kdn antibodies to be directed against Kdn-sialoglycans structurally similar to those on human cell surface Neu5Ac-sialoglycans. Anti-Kdn-glycan antibodies appear during infancy in a pattern similar to those generated following incorporation of the nonhuman Sia N-glycolyl-neuraminic acid (Neu5Gc) onto the surface of nontypeable Haemophilus influenzae (NTHi), a human commensal and opportunistic pathogen. NTHi grown in the presence of free Kdn took up and incorporated the Sia into its lipooligosaccharide (LOS). Surface display of the Kdn within NTHi LOS blunted several virulence attributes of the pathogen, including Neu5Ac-mediated resistance to complement and whole blood kill-ing, complement C3 deposition, IgM binding, and engagement of Siglec-9. Upper air-way administration of Kdn reduced NTHi infection in human-like Cmah null (Neu5Gc-deficient) mice that express a Neu5Ac-rich sialome. We propose a mechanism for the induction of anti-Kdn antibodies in humans, suggesting that Kdn could be a natural and/or therapeutic “Trojan horse” that impairs colonization and virulence phenotypes of free Neu5Ac-assimilating human pathogens. IMPORTANCE All cells in vertebrates are coated with a dense array of glycans often capped with sugars called sialic acids. Sialic acids have many functions, including serving as a signal for recognition of “self” cells by the immune system, thereby guiding an appropriate immune response against foreign “nonself” and/or damaged cells. Several pathogenic bacteria have evolved mechanisms to cloak themselves with sialic acids and evade immune responses. Here we explore a type of sialic acid called “Kdn” (ketodeoxy-nonulosonic acid) that has not received much attention in the past and compare and contrast how it interacts with the immune system. Our results show potential for the use of Kdn as a natural intervention against pathogenic bacteria that take up and coat themselves with external sialic acid from the environment.

DOI： 10.1128/mBio.03226-20

The conserved arginine residue in all siglecs is essential for Siglec-7 binding to sialic acid. 査読有り国際誌

Yoshimura A, Hatanaka R, Tanaka H, Kitajima K, Sato C

Biochemical and biophysical research communications 534 巻頁： 1069 - 1075 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biochemical and Biophysical Research Communications

Siglecs are sialic acid (Sia)-binding immunoglobulin-like lectins; the majority of Siglecs functions as transmembrane receptors on the immune cells via Sia residues. Recently, a new Sia binding site in Siglec-7, termed site 2, where arginine (R) 67 was critical, was identified by computational modeling and biochemical analyses, relative to the primary Sia binding site, termed site 1, containing critical R124. Here, the presence of a new essential R94 residue, which is completely conserved among all identified Siglecs, was demonstrated. A mutation of R94 residue in Siglec-7 led to the disappearance of the Sia binding property, similar to a site 1 mutation (R124A). R94 is close to R67 in site 2, and site 2 mutations at either of them abolished the ligand-binding properties to both gangliosides and glycoproteins. These data suggest that, in addition to site 1, the conserved R residue among Siglecs in site 2 is another functional site.

DOI： 10.1016/j.bbrc.2020.10.023

Comparative Studies of Polysialic Acids Derived from Five Different Vertebrate Brains. 国際誌 Open Access

Yang Y, Murai R, Takahashi Y, Mori A, Hane M, Kitajima K, Sato C

International journal of molecular sciences 21 巻 ( 22 ) 頁： 1 - 22 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

Polysialic acid (polySia/PSA) is a linear homopolymer of sialic acid (Sia) that primarily modifies the neural cell adhesion molecule (NCAM) in mammalian brains. PolySia-NCAM not only displays an anti-adhesive function due to the hydration effect, but also possesses a molecule-retaining function via a direct binding to neurologically active molecules. The quality and quantity of polySia determine the function of polySia-NCAM and are considered to be profoundly related to the maintenance of normal brain functions. In this study, to compare the structures of polySia-NCAM in brains of five different vertebrates (mammals, birds, reptiles, amphibians, and fish), we adopted newly developed combinational methods for the analyses. The results revealed that the structural features of polySia considerably varied among different species. Interestingly, mice, as a mammal, possess eminently distinct types of polySia, in both quality and quantity, compared with those possessed by other animals. Thus, the mouse polySia is of larger quantities, of longer and more diverse chain lengths, and of a larger molecular size with higher negative charge, compared with polySia of other species. These properties might enable more advanced brain function. Additionally, it is suggested that the polySia/Sia ratio, which likely reflects the complexity of brain function, can be used as a new promising index to evaluate the intelligence of different vertebrate brains.

DOI： 10.3390/ijms21228593

Combinational Analyses with Multiple Methods Reveal the Existence of Several Forms of Polysialylated Neural Cell Adhesion Molecule in Mouse Developing Brains. 国際誌 Open Access

Mori A, Yang Y, Takahashi Y, Hane M, Kitajima K, Sato C

International journal of molecular sciences 21 巻 ( 16 ) 頁： 1 - 20 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

Polysialic acid (polySia/PSA) is an anionic glycan polymer of sialic acid, and it mostly modifies the neural cell adhesion molecule (NCAM) in mammalian brains. Quality and quantity of the polySia of the polySia–NCAM is spatio-temporally regulated in normal brain development and functions, and their impairments are reported to be related to diseases, such as psychiatric disorders and cancers. Therefore, precise understanding of the state of polySia–NCAM structure would lead to the diagnosis of diseases for which their suitable evaluation methods are necessary. In this study, to develop these evaluation methods, structures of polySia–NCAM from mouse brains at six different developmental stages were analyzed by several conventional and newly developed methods. Integrated results of these experiments clearly demonstrated the existence of different types of polySia–NCAMs in developing brains. In addition, combinational analyses were shown to be useful for precise understanding of the quantity and quality of polySia, which can provide criteria for the diagnosis of diseases.

DOI： 10.3390/ijms21165892

Discovery of a new sialic acid binding region that regulates Siglec-7. 査読有り国際共著国際誌 Open Access

Yamakawa N, Yasuda Y, Yoshimura A, Goshima A, Crocker PR, Vergoten G, Nishiura Y, Takahashi T, Hanashima S, Matsumoto K, Yamaguchi Y, Tanaka H, Kitajima K, Sato C

Scientific reports 10 巻 ( 1 ) 頁： 8647 - 8647 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Siglec-7 is a human CD33-like siglec, and is localised predominantly on human natural killer (NK) cells and monocytes. Siglec-7 is considered to function as an immunoreceptor in a sialic acid-dependent manner. However, the underlying mechanisms linking sialic acid-binding and function remain unknown. Here, to gain new insights into the ligand-binding properties of Siglec-7, we carried out in silico analysis and site-directed mutagenesis, and found a new sialic acid-binding region (site 2 containing R67) in addition to the well-known primary ligand-binding region (site 1 containing R124). This was supported by equilibrium dialysis, STD-NMR experiments, and inhibition analysis of GD3-binding toward Siglec-7 using synthetic sialoglycoconjugates and a comprehensive set of ganglioside-based glycoconjugates. Our results suggest that the two ligand-binding sites are potentially controlled by each other due to the flexible conformation of the C-C′ loop of Siglec-7.

DOI： 10.1038/s41598-020-64887-4

Effect of expression alteration in flanking genes on phenotypes of St8sia2-deficient mice. 査読有り国際誌 Open Access

Ikegami K, Saigoh K, Fujioka A, Nagano M, Kitajima K, Sato C, Masubuchi S, Kusunoki S, Shigeyoshi Y

Scientific reports 9 巻 ( 1 ) 頁： 13634 - 13634 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) synthesizes polysialic acid (PSA), which is essential for brain development. Although previous studies reported that St8sia2-deficient mice that have a mixed 129 and C57BL/6 (B6) genetic background showed mild and variable phenotypes, the reasons for this remain unknown. We hypothesized that this phenotypic difference is caused by diversity in the expression or function of flanking genes of St8sia2. A genomic polymorphism and gene expression analysis in the flanking region revealed reduced expression of insulin-like growth factor 1 receptor (Igf1r) on the B6 background than on that of the 129 strain. This observation, along with the finding that administration of an IGF1R agonist during pregnancy increased litter size, suggests that the decreased expression of Igf1r associated with ST8SIA2 deficiency caused lethality. This study demonstrates the importance of gene expression level in the flanking regions of a targeted null allele having an effect on phenotype.

DOI： 10.1038/s41598-019-50006-5

Functional roles of ST8SIA3-mediated sialylation of striatal dopamine D(2) and adenosine A(2A) receptors. 査読有り国際共著 Open Access

Lin CY, Lai HL, Chen HM, Siew JJ, Hsiao CT, Chang HC, Liao KS, Tsai SC, Wu CY, Kitajima K, Sato C, Khoo KH, Chern Y

Translational psychiatry 9 巻 ( 1 ) 頁： 209 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Translational Psychiatry

Sialic acids are typically added to the end of glycoconjugates by sialyltransferases. Among the six ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferases (ST8SIA) existing in adult brains, ST8SIA2 is a schizophrenia-associated gene. However, the in vivo substrates and physiological functions of most sialyltransferases are currently unknown. The ST8SIA3 is enriched in the striatum. Here, we showed that ablation of St8sia3 in mice (St8sia3-KO) led to fewer disialylated and trisialylated terminal glycotopes in the striatum of St8sia3-KO mice. Moreover, the apparent sizes of several striatum-enriched G-protein-coupled receptors (GPCRs) (including the adenosine A<inf>2A</inf> receptor (A<inf>2A</inf>R) and dopamine D<inf>1</inf>/D<inf>2</inf> receptors (D<inf>1</inf>R and D<inf>2</inf>R)) were smaller in St8sia3-KO mice than in WT mice. A sialidase treatment removed the differences in the sizes of these molecules between St8sia3-KO and WT mice, confirming the involvement of sialylation. Expression of ST8SIA3 in the striatum of St8sia3-KO mice using adeno-associated viruses normalized the sizes of these proteins, demonstrating a direct role of ST8SIA3. The lack of ST8SIA3-mediated sialylation altered the distribution of these proteins in lipid rafts and the interaction between D<inf>2</inf>R and A<inf>2A</inf>R. Locomotor activity assays revealed altered pharmacological responses of St8sia3-KO mice to drugs targeting these receptors and verified that a greater population of D<inf>2</inf>R formed heteromers with A<inf>2A</inf>R in the striatum of St8sia3-KO mice. Since the A<inf>2A</inf>R-D<inf>2</inf>R heteromer is an important drug target for several basal ganglia diseases (such as schizophrenia and Parkinson’s disease), the present study not only reveals a crucial role for ST8SIA3 in striatal functions but also provides a new drug target for basal ganglia-related diseases.

DOI： 10.1038/s41398-019-0529-z

Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain. 査読有り Open Access

Abe C, Yi Y, Hane M, Kitajima K, Sato C

Scientific reports 9 巻 ( 1 ) 頁： 9950 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Stress is an important environmental factor influencing human behaviour and causing several mental disorders. Alterations in the structure of polysialic acid (polySia/PSA) due to genetic alterations in ST8SIA2, which encodes a polySia-synthesizing enzyme, are related to certain mental disorders. However, whether stress as an environmental factor leads to changes in polySia structure is unknown. Here we studied the effects of acute stress on polySia expression and found reductions in both the quantity and quality of polySia in the olfactory bulb and prefrontal cortex, even with short-term exposure to acute stress. The use of inhibitors for sialidase, microglia and astrocytes revealed that these declines were due to a transient action of sialidase from microglia and astrocytes in the olfactory bulb and prefrontal cortex, respectively. These data suggest that sialidase dynamically regulates polySia expression in a brain region-specific manner.

DOI： 10.1038/s41598-019-46240-6

N-linked mannose glycoconjugates on shrimp thrombospondin, pmTSP-II, and their involvement in the sperm acrosome reaction. 査読有り国際共著

Timklay W, Magerd S, Sato C, Somrit M, Watthammawut A, Senarai T, Weerachatyanukul W, Kitajima K, Asuvapongpatana S

Molecular reproduction and development 86 巻 ( 4 ) 頁： 440 - 449 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Molecular Reproduction and Development

Glycoconjugates in egg extracellular matrices are known to serve several functions in reproductive processes. Here, the presence of N-linked mannose (Man) glycoconjugates on shrimp thrombospondin (pmTSP-II) and their physiological functions were investigated in the black tiger shrimp Penaeus monodon. A molecular analysis of pmTSP-II demonstrated anchorage sites for N-linked glycans in both the chitin-binding and TSP3 domains. The presence of Man residues was verified by concanavalin A lectin histochemistry on the purified fraction of pmTSP-II (250 kDa with protease inhibitor). The function of the Man glycoconjugates was evident by the Con A interference with the pmTSP-II-induced acrosome reaction (AR) as well as by the ability to recover the induction of the AR by the inclusion of Mans in the treatment mixture. In addition, the recombinant proteins of the three signature pmTSP-II domains expressed in E. coli (lacking glycosylation) and mannosidase-treated pmTSP-II showed a minimal ability to initiate the AR response. Together, these results provide evidence of the pivotal role that Man-linked pmTSP-II plays in modulating the shrimp sperm AR, a novel role for a TSP family protein in shrimp reproductive biology.

DOI： 10.1002/mrd.23122

Sialic Acids in Neurology. 査読有り

Sato C, Kitajima K

Advances in carbohydrate chemistry and biochemistry 76 巻頁： 1 - 64 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Advances in Carbohydrate Chemistry and Biochemistry

Sialic acid (Sia) is involved in many biological activities and commonly occurs as a monosialyl residue at the nonreducing terminal end of glycoconjugates. The loss of activity of UDP-GlcNAc2-epimerase/ManNAc kinase, which is a key enzyme in Sia biosynthesis, is lethal to the embryo, which clearly indicates the importance of Sia in embryogenesis. Occasionally, oligo/polymeric Sia structures such as disialic acid (diSia), oligosialic acid (oligoSia), and polysialic acid (polySia) occur in glycoconjugates. In particular, polySia, a well-known epitope that commonly occurs in neuroinvasive bacteria and vertebrate brains, is one of the most well-known and biologically/neurologically important glycotopes in vertebrates. The biological effects of polySia, especially on neural cell-adhesion molecules, have been well studied, and in-depth knowledge regarding polySia has been accumulated. In addition, the importance of diSia and oligoSia epitopes has been reported. In this chapter, the recent advances in the study of diSia, oligoSia, and polySia residues in glycoproteins in neurology, and their history, definition, occurrence, analytical methods, biosynthesis, and biological functions evaluated by phenotypes of gene-targeted mice, biochemical features, and related diseases are described.

DOI： 10.1016/bs.accb.2018.09.003

Structural Biology of Glycans 査読有り

Sato C, Kato K, Yamaguchi Y, Kohda D, Kato R, Suzuki GN K, Kikuchi K, Hirai G, Kizuka Y, Tanaka K, Nakashima Y, Setou M

Glycoscience: Basic Science to Applications 頁： 35 - 63 2019年

Preparation and Properties of a Polycyclic p-Quinodimethane with Two Oxygen Bridges and its Radical Cation in Comparison with the Isomeric o-Quinodimethane. Open Access

Sato C, Suzuki S, Okada K, Kozaki M

Chemistry, an Asian journal 13 巻 ( 23 ) 頁： 3729 - 3736 2018年12月

Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns. 査読有り国際誌 Open Access

Yamakawa N, Vanbeselaere J, Chang LY, Yu SY, Ducrocq L, Harduin-Lepers A, Kurata J, Aoki-Kinoshita KF, Sato C, Khoo KH, Kitajima K, Guerardel Y

Nature communications 9 巻 ( 1 ) 頁： 4647 - 4647 2018年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Communications

The emergence of zebrafish Danio rerio as a versatile model organism provides the unique opportunity to monitor the functions of glycosylation throughout vertebrate embryogenesis, providing insights into human diseases caused by glycosylation defects. Using a combination of chemical modifications, enzymatic digestion and mass spectrometry analyses, we establish here the precise glycomic profiles of eight individual zebrafish organs and demonstrate that the protein glycosylation and glycosphingolipid expression patterns exhibits exquisite specificity. Concomitant expression screening of a wide array of enzymes involved in the synthesis and transfer of sialic acids shows that the presence of organ-specific sialylation motifs correlates with the localized activity of the corresponding glycan biosynthesis pathways. These findings provide a basis for the rational design of zebrafish lines expressing desired glycosylation profiles.

DOI： 10.1038/s41467-018-06950-3

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

Sato C, Hane M

Glycoconjugate journal 35 巻 ( 4 ) 頁： 353 - 373 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Glycoconjugate Journal

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.

DOI： 10.1007/s10719-018-9832-9

酸性糖鎖ポリシアル酸の新機能の発見とその応用展開査読有り Open Access

佐藤ちひろ

化学と生物 56 巻頁： 422 - 431 2018年

Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia. 査読有り Open Access

Fujito NT, Satta Y, Hane M, Matsui A, Yashima K, Kitajima K, Sato C, Takahata N, Hayakawa T

PloS one 13 巻 ( 7 ) 頁： e0200278 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Plos One

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

DOI： 10.1371/journal.pone.0200278

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