文章基本信息

标题：Antioxidant Berberine-Derivative Inhibits Multifaceted Amyloid Toxicity
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作者：Kolla Rajasekhar ; Sourav Samanta ; Vardhaman Bagoband 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：4
页码：1-36
DOI：10.1016/j.isci.2020.101005
语种：English
出版社：Elsevier
摘要：SummaryMultiple lines of evidence indicate that amyloid beta (Aβ) peptide is responsible for the pathological devastation caused in Alzheimer's disease (AD). Aβ aggregation species predominantly contribute to multifaceted toxicity observed in neuronal cells including generation of reactive oxygen species (ROS), mitochondrial dysfunction, interfering with synaptic signaling, and activation of premature apoptosis. Herein, we report a natural product berberine-derived (Ber-D) multifunctional inhibitor to amelioratein cellulomultifaceted toxicity of AD. The structural attributes of polyphenolic Ber-D have contributed to its efficient Cu chelation and arresting the redox cycle to prevent the generation of ROS and rescue biomacromolecules from oxidative damage. Ber-D inhibits metal-dependent and -independent Aβ aggregation, which is supported byin silicostudies. Ber-D treatment averts mitochondrial dysfunction and corresponding neuronal toxicity contributing to premature apoptosis. These key multifunctional attributes make Ber-D a potential therapeutic candidate to ameliorate multifaceted Aβ toxicity in AD.Graphical AbstractDisplay OmittedHighlights•Multifaceted Aβ toxicity activates premature apoptosis and neuronal death in AD•Berberine is modified to nontoxic and polyphenolic multifunctional derivative (Ber-D)•Ber-D modulates Aβ aggregation, metal toxicity, ROS, oxidative and biomolecules damage•Study revealed mitochondrial protection and downregulation of apoptosis markersDrugs; Applied Chemistry; Molecular Biology