Genetic polymorphisms of bone marrow stromal cell antigen-1 (BST-1/CD157): implications for immune/inflammatory dysfunction in neuropsychiatric disorders

Abstract

Bone marrow stromal cell antigen-1 (BST-1/CD157) is an immune/inflammatory regulator that functions as both nicotinamide adenine dinucleotide-metabolizing ectoenzyme and cell-surface signaling receptor. BST-1/CD157 is expressed not only in peripheral tissues, but in the central nervous system (CNS). Although its pathophysiological significance in the CNS is still unclear, clinical genetic studies over a decade have begun revealing relationships between BST-1/CD157 and neuropsychiatric diseases including Parkinson's disease, autism spectrum disorders, sleep disorders, depressive disorders and restless leg syndrome. This review summarizes the accumulating evidence for the involvement of BST-1/CD157 in these disorders.

Keywords: BST-1; CD157; Parkinson’s disease; anxiety; autism spectrum disorder; neuroimmune dysfunction; single-nucleotide polymorphism.

Figure 1

Structure of the human BST-1/CD157 gene and locations of main single-nucleotide-polymorphisms (SNPs). Depicted is the exon-intron organization based on GenBank accession numbers NM_004334 and NC_000004. Black and open boxes represent protein-coding regions and untranslated regions, respectively. The locations of the SNPs on human chromosome 4 (chr4) are indicated in parentheses; numbers after colons represent genomic positions based on the human genome assembly the UCSC GRCh38/hg38 genome browser (http://www.genome.ucsc.edu/cgi-bin/hgGateway?db=hg38). SNPs in black, red and blue stand for those reported to be associated with Parkinson’s disease (PD; representative ones), autism spectrum disorder (ASD) and isolated REM sleep behavior disorder (iRBD), respectively. Single asterisk and double asterisks (in blue) represent association with major depressive disorder (MDD) and restless leg syndrome (RLS), respectively.

Figure 2

Hypothetical scheme for Bst-1/CD157-mediated inflammatory/immune regulation in the CNS. Nucleotide substitution(s) may lower binding affinities of transcription factors (closed circles) to in cis-regulatory regions (open boxes), decrease repressive effects on transcription and thereby upregulate the expression of the BST-1/CD157 gene, presumably in myeloid cells migrated from the periphery and/or microglia. This would disrupt the NAD⁺ homeostasis in the CNS, resulting in sustained immune/inflammatory reaction.