β－淀粉样蛋白（β－amyloid protein ，Aβ）在脑内的异常聚集在阿尔茨海默病（Alzheimer disease ，AD）的发生、发展中扮演着重要的角色。AD患者脑内Aβ代谢失衡，过量的Aβ蛋白会自发形成聚集体，引起神经细胞功能障碍、死亡，最...β－淀粉样蛋白（β－amyloid protein ，Aβ）在脑内的异常聚集在阿尔茨海默病（Alzheimer disease ，AD）的发生、发展中扮演着重要的角色。AD患者脑内Aβ代谢失衡，过量的Aβ蛋白会自发形成聚集体，引起神经细胞功能障碍、死亡，最终导致痴呆。目前研究显示Aβ聚集体主要为寡聚体，原纤维及纤维3种聚集形式，这3种聚集形式的构象不尽相同，对神经细胞造成的损伤方式也有所不同。进一步了解Aβ聚集体的分子结构，有助于对Aβ致病分子机制的认识，为以Aβ为靶点的AD抑制剂开发提供理论基础，本文针对最近关于Aβ聚集体分子结构的研究的前沿进展作一综述。展开更多
The negative-geotaxis climbing assay is used to efficiently study aging and neurodegeneration in Drosophila.To make it suitable for large-scale study,a method called the rapid iterative negative geotaxis（RING） assay...The negative-geotaxis climbing assay is used to efficiently study aging and neurodegeneration in Drosophila.To make it suitable for large-scale study,a method called the rapid iterative negative geotaxis（RING） assay has been established by simultaneously photographing the climbing of multiple groups of flies when they are manually tapped down in test tubes.Here,we automated the assay by using a well-controlled electric motor to drive the tapping,and a homemade program to analyze the climbing height of flies.Using the automated RING（aRING） assay,we found that the climbing ability of a strain of wild-type flies,males in particular,declined rapidly before day 21 after eclosion,but slowly from day 21 to 35.We also found that the expression of arctic mutant Aβ_（42） accelerated the age-dependent decline in the climbing ability of flies.Moreover,using aRING,we examined the effect of third chromosome deficiencies on the accelerated locomotor decline in Aβ_（42）-expressing flies,and isolated 7 suppressors and15 enhancers.展开更多
文摘β－淀粉样蛋白（β－amyloid protein ，Aβ）在脑内的异常聚集在阿尔茨海默病（Alzheimer disease ，AD）的发生、发展中扮演着重要的角色。AD患者脑内Aβ代谢失衡，过量的Aβ蛋白会自发形成聚集体，引起神经细胞功能障碍、死亡，最终导致痴呆。目前研究显示Aβ聚集体主要为寡聚体，原纤维及纤维3种聚集形式，这3种聚集形式的构象不尽相同，对神经细胞造成的损伤方式也有所不同。进一步了解Aβ聚集体的分子结构，有助于对Aβ致病分子机制的认识，为以Aβ为靶点的AD抑制剂开发提供理论基础，本文针对最近关于Aβ聚集体分子结构的研究的前沿进展作一综述。
基金supported by the National Natural Science Foundation of China (81371400 and 81071026)the National Basic Research Development Program of China (2013CB530900)the Key Discipline of Chongming County and Shanghai Institute of Health Science, China (FY(14)700-A5-1-19)
文摘The negative-geotaxis climbing assay is used to efficiently study aging and neurodegeneration in Drosophila.To make it suitable for large-scale study,a method called the rapid iterative negative geotaxis（RING） assay has been established by simultaneously photographing the climbing of multiple groups of flies when they are manually tapped down in test tubes.Here,we automated the assay by using a well-controlled electric motor to drive the tapping,and a homemade program to analyze the climbing height of flies.Using the automated RING（aRING） assay,we found that the climbing ability of a strain of wild-type flies,males in particular,declined rapidly before day 21 after eclosion,but slowly from day 21 to 35.We also found that the expression of arctic mutant Aβ_（42） accelerated the age-dependent decline in the climbing ability of flies.Moreover,using aRING,we examined the effect of third chromosome deficiencies on the accelerated locomotor decline in Aβ_（42）-expressing flies,and isolated 7 suppressors and15 enhancers.
