Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease
Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease
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DOI：
10.3233/jad-160574
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Ariga, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Kitamura, Yoshihisa;Inden, Masatoshi;Ariga, Hiroyoshi
以前，DJ-1调节剂UCP 0054278/comp-B是通过虚拟筛选鉴定的，其中comp-B与DJ-1相互作用，在帕金森病模型中产生抗氧化和神经保护反应。然而，comp-B在体内阿尔茨海默病（AD）模型中的作用尚未确定。因此，我们在AD转基因小鼠模型中研究了comp-B对空间学习、记忆和淀粉样蛋白β（A β）清除的影响。我们发现comp-B解决了认知缺陷，降低了不溶性A β（42）水平，并防止了突触功能的退化，从而表明comp-B可能成为AD治疗的主要化合物。
Previously, DJ-1 modulator UCP0054278/comp-B was identified by virtual screening, where comp-B interacts with DJ-1 to produce antioxidant and neuroprotective responses in Parkinson's disease models. However, the effect of comp-B in an in vivo Alzheimer's disease (AD) model is yet undetermined. Thus, we examined the effect of comp-B on spatial learning, memory, and amyloid-beta (A beta) clearance in a transgenic mouse model of AD. We found that comp-B resolved the cognitive deficits, reduced insoluble A beta(42) levels, and prevented the degeneration of synaptic functions, thereby suggesting that comp-B may become a major compound for AD treatment.