nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story

 Li‑Juan Zhu1  · Fei Li3  · Dong‑Ya Zhu2
1 Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing 210009, China 
2 Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China 
3 Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

nNOS; nNOS-PSD95; nNOS-CAPON; nNOS-SERT; Neurological and neuropsychiatric disorder