Novel anti-alzheimer's dimers:cellular mechanisms of neuroprotection through multiple targets

来源 :中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the | 被引量 : 0次 | 上传用户:jiangshuang_1975
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  Alzheimers disease (AD),.which slowly destroys the victims memory and thinking skills,is one of the leading disorders that impacts millions of the elderly worldwide.Since multi-factorial etiopathogenesis is clearly indicated in AD,multiple drug therapy will be required to address the varied pathological aspects of this disease.Current one-compound-one-target approaches offer limited and transient benefits to AD patients but do not delay the course of neurodegeneration significantly.One-compound-multiple-target drugs urgently need to be developed for preventing and treating AD.Over the past few years,several highly promising anti-Alzheimers dimers have been developed which are derived from homoor hetero-dimers of tacrine and/or huperzine A,a novel alkaloid discovered from the Chinese herb.Our series of studies have shown that relative to the existing anti-AD drugs approved by FDA in the USA,these novel dimers possess greater in vivo acetylcholinesterase inhibition,memory enhancement and multiple neuroprotective activities against the oligomers of β-amyloid,H2O2 and glutamate toxicity through the concurrent blockade of L-type calcium channels,NMDA receptors and neuronal NOS.The results suggest that these novel dimers can be highly promising candidates for the new generation of multi-functional AD therapeutics and neuroprotectants.
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