由神经元和神经胶质细胞组成的神经回路有助于建立中枢神经系统的所有功能。小胶质细胞是中枢神经系统的常驻免疫细胞，具有 UDP 敏感的 P2Y6 受体 (P2Y6R)，可调节个体发育过程中过度突触的吞噬/修剪，并在成年期间以活动依赖性方式细化突触。此外，这种类型的受体在原发性（阿尔茨海默病、帕金森病、神经性疼痛）和继发性（癫痫、缺血性、机械性或辐射引起的）神经变性中起着决定性作用。 P2Y6R 控制的一系列小胶质细胞细胞因子，例如白细胞介素 IL-1β、IL-6、IL-8 和肿瘤坏死因子-α (TNF-α)，会导致神经炎症，从而导致神经变性。因此，P2Y6Rs 的小分子拮抗剂和该受体的基因敲除提供了减轻炎症引起的神经系统疾病的可行方法，但也可能干扰突触回路的调节。本综述旨在研究 P2Y6R 在小胶质细胞中的双重作用，既通过靶向吞噬作用塑造神经回路，又通过多种转导机制促进神经炎症，从而促进神经退行性疾病。© 2024。作者。

Neural circuits consisting of neurons and glial cells help to establish all functions of the CNS. Microglia, the resident immunocytes of the CNS, are endowed with UDP-sensitive P2Y6 receptors (P2Y6Rs) which regulate phagocytosis/pruning of excessive synapses during individual development and refine synapses in an activity-dependent manner during adulthood. In addition, this type of receptor plays a decisive role in primary (Alzheimer's disease, Parkinson's disease, neuropathic pain) and secondary (epilepsy, ischemic-, mechanical-, or irradiation-induced) neurodegeneration. A whole range of microglial cytokines controlled by P2Y6Rs, such as the interleukins IL-1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α), leads to neuroinflammation, resulting in neurodegeneration. Hence, small molecular antagonists of P2Y6Rs and genetic knockdown of this receptor provide feasible ways to alleviate inflammation-induced neurological disorders but might also interfere with the regulation of the synaptic circuitry. The present review aims at investigating this dual role of P2Y6Rs in microglia, both in shaping neural circuits by targeted phagocytosis and promoting neurodegenerative illnesses by fostering neuroinflammation through multiple transduction mechanisms.© 2024. The Author(s).