Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, 12 Smętna Street, Poland.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110349. doi: 10.1016/j.pnpbp.2021.110349. Epub 2021 May 13.
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.
目前，针对神经疾病（如缺血和神经退行性疾病）和精神疾病（如抑郁症），尚无有效的治疗方法，这些疾病都存在谷氨酸/GABA 平衡紊乱和明显的兴奋性毒性。因此，对于这些疾病，寻找新的、有效的治疗策略势在必行。近年来的研究表明，神经肽 Y（NPY）能系统可能是神经保护或抗抑郁化合物的潜在治疗靶点。本综述重点关注 Y2 和 Y5 受体（YRs）在神经疾病（如缺血、阿尔茨海默病、帕金森病、亨廷顿病）和精神疾病（如抑郁症）中的神经保护作用。它总结了目前关于 Y2R 和 Y5R 配体产生神经保护或抗抑郁样作用的潜在机制的相关知识。本综述还讨论了作用于 Y2R 和 Y5R 的配体及其作为体内药理学工具的局限性。本文讨论的临床前研究结果可能有助于开发治疗神经疾病和精神疾病的有效治疗策略，为开发新型 Y2R 和 Y5R 配体作为这些疾病的候选药物铺平道路。
