Lattanzi Roberta, Severini Cinzia, Maftei Daniela, Saso Luciano, Badiani Aldo
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.
Institute of Biochemistry and Cell Biology, IBBC, CNR, Rome, Italy.
Front Pharmacol. 2021 Mar 1;12:640441. doi: 10.3389/fphar.2021.640441. eCollection 2021.
The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.
促动力蛋白（PK）家族，即促动力蛋白1和Bv8/促动力蛋白2（PROK2），最初作为胃肠动力调节剂被发现，它与两种G蛋白偶联受体PKR1和PKR2相互作用，调节昼夜节律、新陈代谢、血管生成、神经发生、肌肉收缩、造血、免疫反应、生殖和痛觉等重要生物学功能。PROK2和PK受体，尤其是PKR2，广泛分布于中枢神经系统的神经元和神经胶质细胞中。一系列病理损伤，如缺氧、活性氧、β淀粉样蛋白和兴奋性毒性谷氨酸，可使PROK2表达水平升高。这表明，参与导致神经元死亡的不同细胞过程的PK系统，可能是神经/神经退行性疾病的关键介质。虽然PROK2/PKRs在生理过程中的许多作用已被记录，但它们在神经病理状态下的作用尚未完全阐明，因为PROK2在神经退行性变或神经保护的潜在机制中可能具有双重功能。在此，我们简要概述了不同病理损伤后PROK2及其同源受体调节的最新研究结果，提供了它们在不同病理条件下相反的神经毒性和神经保护作用的相关信息。
