Research progress in NOS1AP in neurological and psychiatric diseases

Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP, previously named CAPON) was firstly identified in rat brain in 1998. Structurally, NOS1AP consists of a phosphotyrosine-binding (PTB) domain at its N-terminal and a PDZ (PSD-95/discs-large/ZO-1) ligand motif at its C-terminal. The PTB domain of NOS1AP mediates the interactions with Dexras1, scribble, and synapsins. The PDZ ligand motif of NOS1AP binds to the PDZ domain of NOS1, the enzyme responsible for nitric oxide synthesis in the nervous system. NOS1AP is implicated in Dexras1 activation, neuronal nitric oxide production, Hippo pathway signaling, and dendritic development through the association with these important partners. An increasing body of evidence is pointing to the significant roles of NOS1AP in excitotoxic neuronal damage, traumatic nervous system injury, bipolar disorder, and schizophrenia. However, the study progress in NOS1AP in neurological or psychiatric diseases, has not been systematically reviewed. Here we introduce the expression, structure, and isoforms of NOS1AP, then summarize the physiological roles of NOS1AP, and discuss the relationships between NOS1AP alterations and the pathophysiology of some neurological and psychiatric disorders. The review will promote the further investigation of NOS1AP in brain disorders and the development of drugs targeting the NOS1AP PTB domain or PDZ-binding motif in the future.