Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly con...Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.展开更多
目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,...目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,每组各19例,对照组患者给予多巴丝肼片,实验组在对照组的基础上给予银杏叶提取物片,治疗连续4周。治疗结束后,对所有患者黑质DMT1、grp75及认知功能进行检测。结果与治疗前相比,治疗后2组患者的黑质DMT1水平较低(P<0.05);与对照组相比,实验组患者治疗后黑质DMT1水平较低(P<0.05)。与治疗前相比,治疗后2组患者的grp75水平较高(P<0.05),与对照组相比,实验组患者治疗后grp75水平较高(P<0.05)。与治疗前相比,治疗后2组患者的Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05);与对照组相比,实验组患者治疗后Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05)。结论银杏叶提取物能够显著降低帕金森患者黑质DMT1水平,升高grp75水平,改善认知功能。展开更多
文摘Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.
文摘目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,每组各19例,对照组患者给予多巴丝肼片,实验组在对照组的基础上给予银杏叶提取物片,治疗连续4周。治疗结束后,对所有患者黑质DMT1、grp75及认知功能进行检测。结果与治疗前相比,治疗后2组患者的黑质DMT1水平较低(P<0.05);与对照组相比,实验组患者治疗后黑质DMT1水平较低(P<0.05)。与治疗前相比,治疗后2组患者的grp75水平较高(P<0.05),与对照组相比,实验组患者治疗后grp75水平较高(P<0.05)。与治疗前相比,治疗后2组患者的Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05);与对照组相比,实验组患者治疗后Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05)。结论银杏叶提取物能够显著降低帕金森患者黑质DMT1水平,升高grp75水平,改善认知功能。
文摘利用机载Ka波段云雷达(Airborne Ka-Band Precipitation Cloud Radar, KPR)和粒子测量系统(Droplet Measurement Technologies, DMT),分析了2018年4月22日黄淮气旋背景系统下积层混合云中对流泡的动力和微物理特征。首先,对Ka波段云雷达观测的山东地区春季36个对流泡样本按照回波强度、水平尺度、回波顶高三个参量进行统计,结果表明平均回波强度为20~30 d BZ的对流泡占69%。对流泡水平尺度为15~30 km,占61%。对流泡最大回波顶高集中在6~8 km,比周边层云高2~4 km。之后,对4月22日积层混合云中的对流泡个例微物理参数进行统计,结果表明对流泡内部以上升气流为主,最大上升气流速度达到1.35 m s^-1,平均上升气流速度为0.22 m s^-1;对流泡内过冷水含量比较高,最大含水量为0.34 g m^-3,平均含水量为0.15 g m^-3。对流泡内冰晶数浓度是泡外的5.5倍,平均直径是泡外的1.7倍。结合云粒子图像探头,发现对流泡前沿和尾部冰粒子以柱状和辐枝状为主,而对流泡核心区域冰粒子以聚合体形式存在。冰粒子通过凇附过程和碰并过程增长,过冷水含量不足时冰粒子的凇附增长形成柱状粒子,含量充足时可迅速凇附成霰粒子。对流泡内降水形成的微物理机制不完全相同,主要依赖过冷水含量。当云中有充足的过冷水分布时,高层冰晶通过凇附增长形成霰粒子,通过融化层后形成降水;当云中缺少过冷水时,降水的形成主要通过水汽凝华过程形成冰雪晶,然后雪晶通过聚合过程实现增长。
