摘要
Metal ion-induced aggregation of A beta into insoluble plaques is a centralfactor in Alzheimer's disease.Zn^(2+) is the only physiologically available transition metal ionresponsible for aggregating A beta at pH 7.4.To make it clear that the neurotoxicity ofZn^(2+)-induced aggregation of A beta on neurons is the key to understand A beta mechanism of actionfurther.In this paper,we choose A/?(10-21) as the model fragment to research hippocampal CA1pyramidal neurons.For the first time,we adopt the combination of spectral analysis with patch-clamptechnique for the preliminary study of the mutual relations of Zn^(2+),A beta and ion channel fromthe cell level.The following expounds upon the effects and mode of action of two forms (unaggregatedand aggregated) of A beta(10-21) on hippocampus outward potassium channel three processes(activation,inactivation and reactivation).It also shows the molecular mechanics of AD from thechannel level.These results are significant for the further study of A beta nosogenesis and thedevelopment of new types of target drugs for the treatment of AD.
Metal ion-induced aggregation of Aβ into insoluble plaques is a central factor in Alzheimer’s disease. Zn2+ is the only physiologically available transition metal ion responsible for aggregating Aβ at pH 7.4. To make it clear that the neurotoxicity of Zn2+-induced aggregation of Aβ on neurons is the key to un- derstand Aβ mechanism of action further. In this paper, we choose Aβ (10-21) as the model fragment to research hippocampal CA1 pyramidal neurons. For the first time, we adopt the combination of spectral analysis with patch-clamp technique for the preliminary study of the mutual relations of Zn2+, Aβ and ion channel from the cell level. The following expounds upon the effects and mode of action of two forms (unaggregated and aggregated) of Aβ (10-21) on hippocampus outward potassium channel three processes (activation, inactivation and reactivation). It also shows the molecular mechanics of AD from the channel level. These results are significant for the further study of Aβ nosogenesis and the devel- opment of new types of target drugs for the treatment of AD.
基金
Supported by the National Natural Science Foundation of China (Grant Nos. 30470408 and 20637010)
