Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.
Bottom Line: We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain.Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro.In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain.
Affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.Show MeSH
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Mentions: We next analyzed the ability of triptolide to modulate the levels and activity of antioxidant enzymes [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)] and the oxidative products of lipids and proteins [malondialdehyde (MDA) and protein carbonyl groups, respectively]. Treatment with triptolide prevented the decrease in the activity of GSH-Px, the expression of CAT and SOD in the cortex (Fig. 7A–C), and CAT levels in the hippocampus (Fig. 7F). By contrast, the activity of GSH-Px and the expression of SOD in the hippocampus were comparable in the three groups (Fig. 7E,G). In addition, triptolide reduced the production of the oxidative marker MDA in the cortex and hippocampus of 5XFAD mice by ~50% (Fig. 7D,H). Protein carbonyls, which represent the extent of protein oxidation, were upregulated in the brains of 5XFAD mice, and treatment with triptolide partially reversed these effects (Fig. 7I,J). Triptolide therefore increased the activities of anti-oxidative enzymes and subsequently reduced the production of oxidative markers in the brains of 5XFAD mice.
Affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.