Nogo-66 promotes [beta]-amyloid protein secretion via NgR/ROCK-dependent BACE1 activation

The generation of [beta]-amyloid protein (A[beta]) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that Nogo-A may be involved in AD and may regulate the...

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Veröffentlicht in:Molecular medicine reports 2021-03, Vol.23 (3)
Hauptverfasser: Xie, Qing-qing, Feng, Xiao, Huang, Yi-yun, Fang, Nian, Yi, Hua, Wang, Zi-jian, Cao, Qiao-yu, Lou, Guo-feng, Pan, Jun-ping, Hu, Yang, Li, Fang-cheng, Zheng, Qing, Xiao, Fei
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Sprache:eng
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Zusammenfassung:The generation of [beta]-amyloid protein (A[beta]) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that Nogo-A may be involved in AD and may regulate the generation of A[beta]. Nogo-A is known to act as a major inhibitor of neuron regeneration in the adult central nervous system. A recent study indicated that Nogo-A is associated with AD; however, the underlying effect and molecular mechanisms remain largely elusive. In the present study, the potential effects of Nogo-A on AD were investigated. ELISA was used to detect the levels of A[beta], enzymatic activity detection kits were used to determine the activity of secretase enzymes in amyloid precursor protein (APP) metabolism, and western blot analysis was used to detect the expression levels of proteins associated with the APP processing and Nogo-A/Nogo-66 receptor (NgR) signaling pathways. The results revealed that Nogo-66, the major inhibitory region of Nogo-A, promoted neuronal A[beta] secretion by increasing the activity of [beta]-secretase 1 via the NgR/Rho-associated coiled-coil containing kinases pathway in a dose-dependent manner. The present data suggested that Nogo-A may facilitate the onset and development of AD by promoting A[beta] secretion, providing information on a potential novel target for AD therapy. Key words: Nogo-A, Nogo-66 receptor, [beta]-amyloid, [beta]-secretase 1, Alzheimer's disease
ISSN:1791-2997
DOI:10.3892/mmr.2021.11827