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.

目前对于神经系统疾病（缺血和神经退行性疾病）或精神疾病（抑郁症）都没有有效的治疗方法，其中 Glu/GABA 平衡被扰乱并伴有显着的兴奋性毒性。因此，寻找新的有效治疗策略对于这些疾病势在必行。过去几年进行的研究表明，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。这篇综述的重点是 Y2 和 Y5 受体 (YRs) 在神经系统疾病（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。它总结了当前关于 Y2R 和 Y5R 配体的神经保护或抗抑郁样作用的可能机制的知识。该综述还讨论了作用于 Y2R 和 Y5R 的配体及其局限性体内药理学工具。

这里讨论的临床前研究结果可能有助于制定有效的治疗策略，一方面治疗神经系统疾病，另一方面治疗精神疾病，并可能为开发新的 Y2R 和 Y5R 配体作为候选药物铺平道路治疗这些疾病。