Role of Semaphorin 3A in common psychiatric illnesses such as schizophrenia, depression, and anxiety

With societal development and an ageing population, psychiatric disorders have become a common cause of severe and long-term disability and socioeconomic burdens worldwide. Semaphorin 3A (Sema-3A) is a secreted glycoprotein belonging to the semaphorin family. Sema-3A is well known as an axon guidance factor in the neuronal system and a potent immunoregulator at all stages of the immune response. It is reported to have various biological functions and is involved in many human diseases, including autoimmune diseases, angiocardiopathy, osteoporosis, and tumorigenesis. The signals of sema-3A involved in the pathogenesis of these conditions, are transduced through its cognate receptors and diverse downstream signalling pathways. An increasing number of studies show that sema-3A plays important roles in synaptic and dendritic development, which are closely associated with the pathophysiological mechanisms of psychiatric disorders, including schizophrenia, depression, and autism, suggesting the involvement of sema-3A in the pathogenesis of mental diseases. This indicates that mutations in sema-3A and alterations in its receptors and signalling may compromise neurodevelopment and predispose patients to these disorders. However, the role of sema-3A in psychiatric disorders, particularly in regulating neurodevelopment, remains elusive. In this review, we summarise the recent progress in understanding sema-3A in the pathogenesis of mental diseases and highlight sema-3A as a potential target for the prevention and treatment of these diseases.