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Idebenone decreases aβ pathology by modulating rage/caspase-3 signaling and the aβ degradation enzyme nep in a mouse model of ad

Title
Idebenone decreases aβ pathology by modulating rage/caspase-3 signaling and the aβ degradation enzyme nep in a mouse model of ad
Authors
Lee, Hyun-JuJeong, Ha-RamPark, Jin-HeeHoe, Hyang-Sook
DGIST Authors
Lee, Hyun-Ju; Jeong, Ha-Ram; Park, Jin-Hee; Hoe, Hyang-Sook
Issue Date
2021-09
Citation
Biology, 10(9)
Type
Article
Author Keywords
5xFADADAM17Alzheimer’s diseaseIdebenoneNEP
ISSN
2079-7737
Abstract
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 Aβ plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Aβ degradation enzyme NEP and α-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3βY216 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
URI
http://hdl.handle.net/20.500.11750/15851
DOI
10.3390/BIOLOGY10090938
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
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