Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes in vitro.
Neuropharmacology
; 141: 283-295, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30205103
ABSTRACT
Alzheimer's disease (AD) is a pathology characterized by the abnormal accumulation of amyloid-beta (Aß) and hyperphosphorylated tau. Oxidative stress and neuroinflammation are also strongly related to this disease. The ability of two new glycosylated angucyclinones, streptocyclinones A and B (1 and 2), isolated from Streptomyces sp to improve AD hallmarks was evaluated. Compounds were able to protect SH-SY5Y neuroblastoma cells from H2O2-induced oxidative injury by activating the nuclear factor E2-related factor (Nrf2). Their capacity to modulate neuroinflammation was tested in lipopolysaccharide-activated BV2 microglial cells. Compounds reduced the release of pro-inflammatory factors, inhibited the activation of NFκB and mitogen activated kinases (MAPK), and induced the translocation of Nrf2 to the nucleus of microglial cells. A trans-well co-culture was established to determine the effect of microglia treated with streptocyclinones on the survival of SH-SY5Y cells. The cell viability of neuroblastoma cells increased when the compounds were added to BV2 cells. SH-SY5Y-TMHT441â¯cells were used to determine the effect of compounds on tau phosphorylation. Both compounds reduced tau hyperphophorylation by targeting MAPK kinases. Moreover, streptocyclinone B (2) was able to inhibit the activity of ß-secretase 1 and decrease the release of reactive oxygen species in BV2 cells stimulated with Aß. With the same co-culture trans-well system, the treatment of Aß-stimulated microglia with compound 2 augmented the viability of SH-SY5Y-TMHT441â¯cells. The results presented in this work provide evidences of the multitarget activities displayed by these new Streptomyces compounds, making them good candidates for further studies in the treatment of AD.
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Base de dados:
MEDLINE
Assunto principal:
Antraquinonas
/
Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neuropharmacology
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Espanha