Siglecs-mediated immune regulation in neurological disorders

The surfaces of various immune cells are rich in glycan chains, including the sialic-acid-binding immunoglobulin-like lectins (Siglecs) family. As an emerging glyco-immune checkpoint, Siglecs have the ability to bind and interact with various glycoproteins, thereby eliciting a series of downstream reactions to modulate the immune response. The impact of Siglecs has been extensively studied in tumor immunotherapy. However, research in neurological disorders and neurological diseases is very limited, and therapeutic options involving Siglecs need further exploration. Siglecs play a crucial role in the development, homeostasis, and repair processes of the nervous system, especially in degenerative diseases. This review summarizes studies on the immunomodulatory role mediated by Siglecs expressed on different immune cells in various neurological disorders, elucidates how dysregulated sialic acid contributes to several psychiatric disorders, and discusses the progress and limitations of research on the treatment of neurological disorders.