Can small molecule inhibitors of glutaminyl cyclase be used as a therapeutic for Alzheimer's disease?

Can small molecule inhibitors of glutaminyl cyclase be used as a therapeutic for Alzheimer's disease?
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DOI:
10.4155/fmc-2017-0190
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发表时间:
2017-10
影响因子:
4.2
通讯作者:
Haiqiang Wu
Haiqiang Wu
中科院分区:
医学3区
文献类型:
--
作者:
Haiqiang Wu

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Alzheimer's disease (AD) is a multifactorial and socioeconomically burdensome disease. In view of the failures of anti-AD candidates, we should try to rethink what we did before and what we should do next, in part at least. Research shows that the more neurotoxic factor, pyroglutamate-Aβs, and the more important inflammatory mediators, pyroglutamate-CCL2, both contribute to the initiation of AD specifically and the generation of N-terminal intramolecular cyclization catalyzed by glutaminyl cyclase quality control, the over-expression of which correlates positively with the severity of AD. Subsequently, lowering pyroglutamate-Aβs and pyroglutamate-CCL2 levels by quality control inhibition using small molecule inhibitors could be expected as an amazing strategy for the prevention and treatment of AD.