茶多酚在帕金森病中的神经保护作用研究进展

帕金森病(Parkinson’s disease,PD)是一种常见的神经退行性疾病.茶叶中特有的多酚类物质在预防神经退行性疾病方面具有重要作用.大量的体外研究表明,茶多酚在PD中通过抗氧化、铁螯合、抑制α-突触核蛋白聚集和调节细胞内信号通路等机制发挥神经保护作用.综述了茶多酚在PD模型动物和临床研究中的神经保护作用,对今后茶多酚在抗PD的研究中存在的问题和发展趋势给出了建议.     

熊果酸在神经精神系统疾病中的药理作用及机制研究进展

 熊果酸（ursolic acid,UA）是一种五环三萜类化合物,存在于熊果、女贞叶、枇杷叶等植物中。熊果酸不仅具有抗氧化、抗炎、抗肿瘤、抗糖尿病、保肝等药理活性,还具有改善和治疗多种神经精神系统疾病的作用。通过文献分析,归纳总结了熊果酸在神经元损伤、脑血管疾病和精神障碍中的药理作用及其作用机制的研究进展。     

黄藤水提物对AD果蝇疗效和寿命的影响

探讨黄藤水提物对AD果蝇疗效和寿命的影响。Elav-gal4基因型雌性果蝇和UAS-Aβ42基因型雄性果蝇进行杂交,收集三天内子代Elav-gal4 >> UAS-Aβ42雄性果蝇,利用UAS-Aβ42/cyo雄性果蝇作为对照,实验组果蝇和对照组果蝇放置在浓度为0、0.5、1、2 mg/mL的黄藤水提物培养基中饲养0、7、14 d,观察爬管实验阳性的果蝇数量,并每天计数果蝇的死亡数直至全部果蝇死亡,计算果蝇平均寿命。结果表明黄藤水提物浓度为0.5 mg/mL饲养7 d和14 d时,与对照组相比,AD果蝇的神经行为学表现和存活时间有改善作用,但效果不显著（P＞0.05）;浓度增加到1 mg/mL时,实验组饲养7 d和14 d爬管实验阳性的果蝇数量与对照组相比均有所上升（P＜0.05）,并且延缓果蝇死亡时间,延长果蝇寿命（P＜0.05）;然而随着浓度的增加,饲养7 d和14 d的果蝇爬管行为学与对照组相比均有明显的抑制作用（P＜0.05）,果蝇的生存时间也显著减少（P＜0.01）。此次实验还发现黄藤水提物在低浓度时治疗AD作用并不明显,但超过2 mg/mL时对AD果蝇爬管行为学和寿命均产生不利影响,因此只有在剂量和给药天数均合适的情况下才会产生积极作用。     

Neuroactive steroids: State of the art and new perspectives

Neuroactive steroids include synthetic steroidal compounds and endogenous steroids, produced by endocrine glands (hormonal steroids) or the nervous tissue (neurosteroids), which regulate neural functions. These steroids bind to nuclear receptors or act through the activation of membrane-associated signaling pathways to modulate various important processes including the development of the nervous system, neural plasticity and the adaptive responses of neurons and glial cells under pathological conditions. Reviewed and updated in the present paper are the pleiotropic and protective abilities of neuroactive steroids. The fundamental evidence and knowledge gained constitute a profound background that offers interesting possibilities for developing effective strategies against several disorders of the nervous system. Received 3 September 2007; received after revision 24 October 2007; accepted 29 October 2007     

Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid neurotoxicity and its consequences. Received 26 January 2006; received after revision 24 March 2006; accepted 12 April 2006     

氧气的适应性机制及低氧预适应研究进展

 氧气是有氧代谢和能量产生的必要条件,对于大多数生物来说都是必不可少的。过多或过少的氧气都可能危害生命,因此研究生物快速响应变化的氧气水平的机制至关重要。当氧气需求超过氧气供应时,细胞就会变得低氧。介绍了氧气的特性以及生理、病理条件下低氧的适应机制,论述了低氧作为的积极方面--低氧预适应的历史和研究进展,展望了低氧预适应在高空、高原等极端环境中以及在卒中等相关临床疾病中的治疗前景。     

Alzheimer’s disease: the impact of age-related changes in reproductive hormones

Two classes of ovarian steroids, estrogens and progestins, are potent in protecting neurons against acute toxic events as well as chronic neurodegeneration. Herein we review the evidence for neuroprotection by both classes of steroids, provide plausible mechanisms for these potent neuroprotective activities and indicate the need for further clinical trials of both estrogens and progestins in protection against acute and chronic conditions that cause neuronal death. Estrogens at concentrations ranging from physiological to pharmacological are neuroprotective in a variety of in vitro and in vivo models of cerebral ischemia and brain trauma as well as in reducing key neuropathologies of Alzheimers disease. While the mechanisms of this potent neuroprotection are currently unresolved, a mitochondrial mechanism is involved. Progestins have been recently shown to activate many of the signaling pathways used by estrogens to neuroprotect, and progestins have been shown to protect against neuronal loss in vitro and in vivo in a variety of models of acute insult. Collectively, results of these animal and tissue culture models suggest that the loss of both estrogens and progestins at the menopause makes the brain more vulnerable to acute insults and chronic neurodegenerative diseases. Further clinical assessment of appropriate regimens of estrogens, progestins and their combination are supported by these data.     

Protein phosphatases and their potential implications in neuroprotective processes

Several neurological disorders such as stroke, amyotrophic lateral sclerosis and epilepsy result from excitotoxic events and are accompanied by neuronal cell death. These processes engage multiple signalling pathways and recruit numerous molecular components, in particular several families of protein kinases and protein phosphatases. While many investigations have examined the importance of protein kinases in excitotoxicity, protein phosphatases have not been well studied in this context. However, recent advances in understanding the functions of protein phosphatases have suggested that they may play a neuroprotective role. In this review, we summarize some of the recent findings that illustrate the pleiotropic and complex functions of tyrosine and serine/threonine protein phosphatases in the cascade of events leading to neuronal cell death, and highlight their potential intervention in limiting the extent of neuronal death.Received 8 January 2005; received after revision 3 March 2005; accepted 14 March 2005     

Neuroglobin,seven years after

Neuroglobin is expressed in vertebrates brain and belongs to a branch of the globin family that diverged early in evolution. Sequence conservation suggests a relevant role in the nervous system, with tight structural restraints. Experiments in vivo and in vitro showed increased hypoxic stress damage upon repressing neuroglobin biosynthesis and improved recovery following overexpression. Neuroglobin shows internal heme hexacoordination, which controls oxygen affinity and kinetics. Neuroglobin concentration, oxygen affinity and enhanced autooxidation question a role in oxygen delivery; thus it was proposed that the neuroprotective effect might be due to radical scavenging or activation of protection mechanisms. Neuroglobin's structure shows a peculiar internal cavity of very large size. Binding of heme ligands is associated to a conformational change involving the heme that "slides" into the pre-existing cavity and makes the sixth coordination position available. These features may pave the way to an understanding of neuroprotection by neuroglobin.