Nogo‑66 promotes β‑amyloid protein secretion via NgR/ROCK‑dependent BACE1 activation.

Autor: Xie QQ; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Feng X; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Huang YΥ; Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Fang N; Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Yi H; Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 511436, P.R. China., Wang ZJ; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Cao QΥ; Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Lou GF; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway., Pan JP; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Hu Y; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Li FC; Department of Neurosurgery, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510632, P.R. China., Zheng Q; Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China., Xiao F; Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Jazyk: angličtina
Zdroj: Molecular medicine reports [Mol Med Rep] 2021 Mar; Vol. 23 (3). Date of Electronic Publication: 2021 Jan 26.
DOI: 10.3892/mmr.2021.11827
Abstrakt: The generation of β‑amyloid protein (Aβ) 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 Aβ. 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 Aβ, 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 Aβ secretion by increasing the activity of β‑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 Aβ secretion, providing information on a potential novel target for AD therapy.
Databáze: MEDLINE
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