Neuropeptide Y Y2 and Y5 receptors as potential targets for neuroprotective and antidepressant therapies: Evidence from preclinical studies

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2021-12, Vol.111, p.110349-110349, Article 110349
• Main Author: Domin, Helena
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - prevention & control; Animals; Antidepressant-like effect; Depression - drug therapy; Depression - prevention & control; Drug Discovery; Humans; Huntington Disease - drug therapy; Huntington Disease - prevention & control; Ischemia - drug therapy; Ischemia - prevention & control; Mice; Neuropeptide Y - pharmacology; Neuroprotection; Neuroprotection - drug effects; NPY; Receptors, Neuropeptide Y - metabolism; Synapses - metabolism; Y2 receptor (Y2R); Y5 receptor (Y5R)
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2021.110349

There is currently no effective treatment either for neurological illnesses (ischemia and neurodegenerative diseases) or psychiatric disorders (depression), in which the Glu/GABA balance is disturbed and accompanied by significant excitotoxicity. Therefore, the search for new and effective therapeutic strategies is imperative for these disorders. Studies conducted over the last several years indicate that the neuropeptide Y (NPY)-ergic system may be a potential therapeutic target for neuroprotective or antidepressant compounds. This review focuses on the neuroprotective roles of Y2 and Y5 receptors (YRs) in neurological disorders such as ischemia, Alzheimer's disease, Parkinson's disease, Huntington's disease, and in psychiatric disorders such as depression. It summarizes current knowledge on the possible mechanisms underlying the neuroprotective or antidepressant-like actions of Y2R and Y5R ligands. The review also discusses ligands acting at Y2R and Y5R and their limitations as in vivo pharmacological tools. The results from the preclinical studies discussed here may be useful in developing effective therapeutic strategies to treat neurological diseases on the one hand and psychiatric disorders on the other, and may pave the way for the development of novel Y2R and Y5R ligands as candidate drugs for the treatment of these diseases. •The neuropeptide Y (NPY)-system is implicated in neurological and psychiatric disorders.•Y2R and Y5R ligands may be effective in neuroprotective and antidepressant therapies.•Y2R and Y5R agonists displayed neuroprotective effects after delayed treatment.•Y2R and Y5R antagonists exhibited antidepressant activity after a single peripheral injection.