Haigh Cathryn L, Tumpach Carolin, Collins Steven J, Drew Simon C
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, 3010, Australia.
Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia.
Cell Biochem Biophys. 2016 Sep;74(3):297-306. doi: 10.1007/s12013-016-0747-4. Epub 2016 Jun 21.
Eight-hydroxyquinolines (8HQs) are a class of compounds that have been identified as potential therapeutics for a number of neurodegenerative diseases. Understanding the influence of structural modifications to the 8HQ scaffold on cellular behaviour will aid the identification of compounds that might be effective in treating dementias. In this study, we describe the action of 2-[(dimethylamino)methyl]-8-hydroxyquinoline (DMAMQ) on adult murine neural stem cells (NSCs) cultured in vitro. Treatment of NSCs with DMAMQ resulted in enhanced self-renewal and increased neurite outgrowth. Concurrent with the positive growth effects was an increase in intracellular reactive oxygen species, with the growth being inhibited by inactivation of the NADPH oxidase (Nox) enzyme family. Our results indicate that DMAMQ can stimulate neurogenesis via the Nox signalling pathway, which may provide therapeutic benefit in treating dementias of various types by replenishing neurones using the brain's own reserves. The narrow concentration range over which these effects were observed, however, suggests that there may exist only a small therapeutic window for neuro-regenerative applications.
8-羟基喹啉（8HQs）是一类已被确定为多种神经退行性疾病潜在治疗药物的化合物。了解对8HQ支架进行结构修饰对细胞行为的影响，将有助于识别可能有效治疗痴呆症的化合物。在本研究中，我们描述了2-[(二甲氨基)甲基]-8-羟基喹啉（DMAMQ）对体外培养的成年小鼠神经干细胞（NSCs）的作用。用DMAMQ处理NSCs导致自我更新增强和神经突生长增加。与积极的生长效应同时出现的是细胞内活性氧的增加，而NADPH氧化酶（Nox）酶家族的失活会抑制这种生长。我们的结果表明，DMAMQ可以通过Nox信号通路刺激神经发生，这可能通过利用大脑自身储备补充神经元来为治疗各种类型的痴呆症提供治疗益处。然而，观察到这些效应的狭窄浓度范围表明，神经再生应用可能仅存在一个小的治疗窗口。
