Multitarget Profiling of a Strigolactone Analogue for Early Events of Alzheimer's Disease: In Vitro Therapeutic Activities against Neuroinflammation

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Tarih

2020

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Amer Chemical Soc

Erişim Hakkı

info:eu-repo/semantics/closedAccess

Özet

Neuropathological changes in Alzheimer's disease (AD) are directly linked to the early inflammatory microenvironment in the brain. Therefore, disease-modifying agents targeting neuroinflammation may open up new avenues in the treatment of AD. Strigolactones (SLs), subclasses of structurally diverse and biologically active apocarotenoids, have been recently identified as novel phytohormones. In spite of the remarkable anticancer capacity shown by SLs, their effects on the brain remained unexplored. Herein, the SIM-A9 microglial cell line was used as a phenotypic screening tool to search for the representative SL, GR24, demonstrating marked potency in the suppression of lipopolysaccharide (LPS)-induced neuroinflammatory/neurotoxic mediators by regulating NF-kappa B, Nrf2, and PPAR gamma signaling. GR24 also in the brain endothelial cell line bEnd.3 mitigated the LPS-increased permeability as evidenced by reduced Evans' blue extravasation through enhancing the expression of tight junction protein, occludin. Collectively, the present work shows the anti-neuroinflammatory and glia/neuroprotective properties of GR24, making SLs promising scaffolds for the development of novel anti-AD candidates.

Açıklama

Anahtar Kelimeler

Alzheimer's disease, neuroinflammation, neuroprotective, microglia, strigolactones, carotenoids

Kaynak

Acs Chemical Neuroscience

WoS Q Değeri

Q2

Scopus Q Değeri

Q1

Cilt

11

Sayı

4

Künye