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Objective To observe the expression and localization of β-site amyloid precursor protein cleaving enzyme 1 (BACEl) in rat superior cervical ganglion and the effect of chronic intermittent frypoxia (CIH) on BACEl level. Methods The expression and distribution of BACEl in superior cervical ganglion were detected by RT-PCR, Western blotting and immunohistochemistry. Totally 16 male SD rats were randomly divided into control group and CIH group, 8 rats in each group. After 2 weeks of modeling, the effect of CIH on BACEl and peroxisome proliferators activated receptor gamma coactivator 1 alpha (PGC-la) mRNA level was detected by RT-PCR. Results BACEl was expressed in rat superior cervical ganglion, and mainly distributed in satellite glial cells and nerve fibers, but not in blood vessels, neurons and small intesely fluorecent(SIF) cells. CIH down-regulated BACEl mRNA level, but up-regulated PGC-la mRNA level ( P < 0.01). Conclusion BACEl is located in satellite glial cells and nerve fibers in the superior cervical ganglion of rats. The decreased level of BACEl ma)' be involved in the regulation of CIH-induced synaptic plasticity of superior cervical ganglion.
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Objective To observe the expression and localization of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in rat adrenal gland and to detect the effect of cyclic intermittent hypoxia (CIH) on the expression of BACE1. Methods The expression and localization of BACE1 in rat adrenal gland were detected by Western blotting and immunohistochemistry. Sixteen male Sprague-Dawley (SD) rats were randomly divided into two groups: control group and CIH group, 8 rats in each group. The protein levels of BACE1 and tyrosine hydroxylase (TH) in rat adrenal medulla were detected by Western blotting after CIH 2 weeks treatment. Results BACE1 was mainly localized in rat adrenal medullary nerve fibers. Compared with the control group, BACE1 protein level decreased and TH protein level increased in the adrenal medulla in the CIH group. Conclusion BACE1 is located in rat adrenal medullary nerve fibers. The decreased level of BACE1 may participate in slowing down the excessive enhancement of sympathetic activity induced by CIH.
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Introduction: Life style of humans, with changes in diet, exercise and life style practices which play an important role in enhancing the progression of age related degenerative problems like dementia. The most common cause of dementia in the world is Alzheimer’s disease which ultimately decrease the cognitive function mainly learning and memory. The objective of the study was to find the multi target potential efficacy of the ligands, Glabridin and Diosmetin in altering the two main molecular targets of Alzheimer’s disease (AD). The target enzymes were amyloid binding alcohol dehydrogenase (ABAD) and β-site amyloid precursor protein cleaving enzyme 1(BACE1). Material and methods: In this study, we analyzed that multitarget potential of the two natural compounds on the two prior target enzymes of Alzheimer’s disease which are mainly involved in producing neurodegeneration. Drug likeness properties, absorption, digestion metabolic and toxicity profile and molecular docking were analyzed to determine therapeutic aspect by virtual methods. Results: Binding energy and Vander Waals force of Diosmetin were higher than Glabridin with the target ABAD and less than with BACE1 which showed that both drugs can be used in modulating the enzyme phosphorylation in Alzheimer’s disease. Conclusion: Glabridin and Diosmetin could be used as promising drug candidates as ABAD inhibitor and BACE1 inhibitor in Alzheimer’s disease
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Objective To explore the effects of electroacupuncture at Baihui (DU20) and Shenting (GV24) on Alzheimer's disease, and possible mechanism for it.Methods A total of 24 eight-month-old APP/PS1 male mice were randomly divided into model group (n = 8), electroacupuncture group (n = 8) and non-acupoint group (n = 8), and other eight wild-type mice were as wild-type group.The electroacupuncture group accepted electroacupuncture at Baihui and Shenting, while the non-acupoint group accepted electroacupuncture at bilateral subcostal non-acupoint area, and the wild-type group and the model group accepted the same grasping and fixing, for 28 days. Then they assessed with Morris water maze test. The levels of β-amyloid protein (Aβ) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in cerebral cortex were detected with immunohistochemistry and immunofluorescence respectively, and the level of BACE1 m RNA with RT-PCR.Results Compared with the model group, the escape latency decreased in the electroacupuncture group (P ＜ 0.001), and the times crossing platforms increased (P ＜ 0.001), while the expression of BACE1 and Aβ decreased (P ＜ 0.001).Conclusion Electroacupuncture may improve the learning-memory ability by inhibiting the expression of BACE1 in the cerebral cortex of APP/PS1 mice to decreasing the level of Aβ.
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Objective • To investigate the effect of microenvironment on the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in PC12 cells. Methods • The PC12 cells were respectively treated with thapsigargin (Tg), lipopolysaccharide (LPS), H2O2, hypoxia incubator and hypoglycemic medium to produce mild endoplasmic reticulum stress (ERS), inflammatory environment, mild oxidative stress, hypoxia and low glucose conditions. Western blotting and fluorescence quantitative PCR were used to detect the expression of BACE1 protein and BACE1 mRNA. Results • After PC12 cells were treated with Tg (0.13 μmol/L) for 12 h or LPS (0.01 mg/mL) for 36 h, BACE1 protein and mRNA levels were significantly up-regulated (P0.05). Conclusion • Mild ERS and inflammatory condition can up-regulate BACE1 mRNA and protein expression in PC12 cells.
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β-secretase，a type I transmembrane aspartic protease, initiates b-amyloid protein(Aβ) formation by cleaving β- amyloid precursor protein between Met596and Asp597or between Tyr606and Glu607to generate N-terminal fragment of Aβ. β-Secretase has many members，and aspartic proteinase β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the most famous of them. Because BACE1 plays a significant role in the pathogenesis of Alzheimer’ s disease (AD) and a neurodegenerative disease# it has been studied fully. In this article，we review the gene and protein structure，transcription and translation，intracellular trafficking and metabolism of BACE1 and summarize substrates and homologous enzymes of BACE1. This work provides some reference for BACE1 as a drug target on AD.
ABSTRACT
β-secretase, a typeⅠtransmembrane aspartic protease, initiates β-amyloid protein(Aβ) formation by cleaving β-amyloid precursor protein between Met596 and Asp597 or between Tyr606 and Glu607 to generate N-terminal fragment of Aβ. β-Secretase has many members,and aspartic proteinaseβ-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the most famous of them. Because BACE1 plays a significant role in the pathogenesis of Alzheimer′s disease (AD) and a neurodegenerative disease, it has been studied fully. In this article, we review the gene and protein structure, transcription and translation, intracellular trafficking and metabolism of BACE1 and summarize substrates and homologous enzymes of BACE1. This work provides some reference for BACE1 as a drug target on AD.