Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro
| العنوان: | Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro |
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| المؤلفون: | Rebeca Alvariño, Eva Alonso, Amparo Alfonso, Luis M. Botana, Rodney Lacret, Olga Genilloud, Fernando Reyes, Daniel Oves-Costales |
| المصدر: | Molecular Pharmaceutics. 16:1456-1466 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Amyloid beta, p38 mitogen-activated protein kinases, Pharmaceutical Science, tau Proteins, 02 engineering and technology, In Vitro Techniques, Pharmacology, medicine.disease_cause, 030226 pharmacology & pharmacy, Neuroprotection, Neuroblastoma, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, medicine, Animals, Viability assay, Neuroinflammation, Inflammation, Amyloid beta-Peptides, biology, Microglia, Chemistry, Kinase, 021001 nanoscience & nanotechnology, Streptomyces, 3. Good health, Oxidative Stress, Neuroprotective Agents, medicine.anatomical_structure, biology.protein, Molecular Medicine, Macrolides, Reactive Oxygen Species, 0210 nano-technology, Oxidative stress |
| الوصف: | The macrolide caniferolide A was isolated from extracts of a culture of the marine-derived actinomycete Streptomyces caniferus, and its ability to ameliorate Alzheimer's disease (AD) hallmarks was determined. The compound reduced neuroinflammatory markers in BV2 microglial cells activated with lipopolysaccharide (LPS), being able to block NFκB-p65 translocation to the nucleus and to activate the Nrf2 pathway. It also produced a decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide release and inhibited iNOS, JNK, and p38 activities. Moreover, the compound blocked BACE1 activity and attenuated Aβ-activation of microglia by drastically diminishing ROS levels. The phosphorylated state of the tau protein was evaluated in SH-SY5Y tau441 cells. Caniferolide A reduced Thr212 and Ser214 phosphorylation by targeting p38 and JNK MAPK kinases. On the other side, the antioxidant properties of the macrolide were determined in an oxidative stress model with SH-SY5Y cells treated with H2O2. The compound diminished ROS levels and increased cell viability and GSH content by activating the nuclear factor Nrf2. Finally, the neuroprotective ability of the compound was confirmed in two trans-well coculture systems with activated BV2 cells (both with LPS and Aβ) and wild type and transfected SH-SY5Y cells. The addition of caniferolide A to microglial cells produced a significant increase in the survival of neuroblastoma in both cases. These results indicate that the compound is able to target many pathological markers of AD, suggesting that caniferolide A could be an interesting drug lead for a polypharmacological approach to the illness. |
| تدمد: | 1543-8392 1543-8384 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae7734c56ea1419fcf012795092ee004Test https://doi.org/10.1021/acs.molpharmaceut.8b01090Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....ae7734c56ea1419fcf012795092ee004 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15438392 15438384 |
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