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近10年来,由于神经影像和分子生物学迅速发展,神经系统变性疾病的诊断取得了长足进步。相比之下,其治疗仍然举步维艰。了解神经变性的细胞和分子机制,寻找真实有效的干预靶点、提高疾病预防和治疗效果是临床神经科学迫切需要解决的现实问题。近年来人们发现诸多神经变性病呈现相似的病理和重叠的临床表现,它们之间存在类似的细胞和分子机制,免疫炎性反应形成的微环境是其共同的细胞学通路,而其中Rho激酶(ROCK)的异常激活可能是其共同的分子机制之一。研究表明通过抑制ROCK的活性能够减少免疫细胞的炎性反应、抑制中枢神经系统一氧化氮(NO)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)等炎性因子产生,改善炎性微环境保护神经元,同时抑制ROCK活性还可促进神经突触再生和神经干细胞动员分化。综上,ROCK抑制剂(Rho kinase inhibitor,RKI)有可能成为神经变性疾病的潜在药物。本文就RKI治疗神经系统变性疾病的潜在可能和相应机制进行简要综述。
In the past 10 years, due to the rapid development of neuroimaging and molecular biology, considerable progress has been made in the diagnosis of degenerative diseases of the nervous system. In contrast, the treatment is still difficult. Understanding the neurodegenerative cell and molecular mechanisms, looking for real and effective intervention targets, and improving the effectiveness of disease prevention and treatment are the real problems urgently needed to be solved in clinical neuroscience. In recent years, it has been found that many neurodegenerative diseases show similar pathological and overlapping clinical manifestations. Similar cellular and molecular mechanisms exist between them, and the microenvironment formed by immune inflammatory reaction is their common cytological pathway. Among them, Rho kinase ROCK) abnormal activation may be one of its common molecular mechanisms. Studies have shown that by inhibiting the activity of ROCK can reduce the inflammatory reaction of immune cells, inhibit central nervous system nitric oxide (NO), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and other inflammatory factors to improve the inflammatory microenvironment protect neurons, while inhibiting ROCK activity can also promote neuronal synaptogenesis and neural stem cell mobilization and differentiation. In conclusion, ROCK kinase inhibitor (RKI) may be a potential drug for neurodegenerative diseases. This article briefly reviews the potential of RKI in the treatment of degenerative diseases of the nervous system and its corresponding mechanisms.