Can Small Molecule Inhibitors of Glutaminyl Cyclase Be Used as a Therapeutic for Alzheimer'S Disease?

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.