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Publication : Idebenone Decreases Aβ Pathology by Modulating RAGE/Caspase-3 Signaling and the Aβ Degradation Enzyme NEP in a Mouse Model of AD.

First Author  Lee HJ Year  2021
Journal  Biology (Basel) Volume  10
Issue  9 PubMed ID  34571815
Mgi Jnum  J:352821 Mgi Id  MGI:7706325
Doi  10.3390/biology10090938 Citation  Lee HJ, et al. (2021) Idebenone Decreases Abeta Pathology by Modulating RAGE/Caspase-3 Signaling and the Abeta Degradation Enzyme NEP in a Mouse Model of AD. Biology (Basel) 10(9)
abstractText  The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood-brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer's disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of idebenone treatment on AD pathology in 5xFAD mice, a model of AD. Idebenone significantly downregulated Abeta plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Abeta degradation enzyme NEP and alpha-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3beta(Y216) levels, thereby inhibiting tau hyperphosphorylation at Thr231 and total tau levels in 5xFAD mice. Taken together, the present study indicates that idebenone modulates amyloidopathy and tauopathy in 5xFAD mice, suggesting therapeutic potential for AD.
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