スプライシング異常から解析する統合失調症

Schizophrenia through analysis of aberrant alternative pre-mRNA splicing

神経細胞やグリア細胞などの神経系細胞の遺伝子発現調節に，選択的スプライシングが重要な役割を演じている．それゆえに，この調節機構の破綻は重篤な発達障害や疾患発現の引き金となる．近年多くの神経変性疾患や精神疾患において種々の遺伝子のスプライシング異常が報告されている．本稿では，最近急速に報告され始めた統合失調症における選択的スプライシングの異常に焦点を当て，最新の情報を紹介しつつ，異常スプライシングを標的とした診断・治療への可能性について解説する．

Alternative pre-mRNA splicing plays a key role in the regulation of gene expression in both neurons and glial cells, and malfunction or dysregulation of the splicing process actually causes developmental abnormalities, leading to the pathological development involved in the eventual diseases.　Schizophrenia is a very common mental disorder but it reveals pathogenic complexity.　Intriguingly, misregulation of alternative splicing of genes associated with neurodevelopment and neurotransmission has been detected in schizophrenia.　In this review, we describe the aberrant splicing of specific genes that are potentially involved in the cause of schizophrenia.　Finally, we discuss the possibility of the diagnosis and treatment of schizophrenia through detecting the characteristic aberrant splicing as the hallmark.