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Multitarget Profiling of a Strigolactone Analogue for Early Events of Alzheimer’s Disease: In Vitro Therapeutic Activities against Neuroinflammation
journal contribution
posted on 2020-02-06, 16:06 authored by Begum Kurt, Adem Ozleyen, Gizem Antika, Yakup Berkay Yilmaz, Tugba Boyunegmez TumerNeuropathological
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-κB, Nrf2, and PPARγ 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.
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Neuroinflammation Neuropathological changesphenotypic screening toolAlzheimercell line bEnd .3 mitigatedLPS-increased permeabilityjunction proteinNFanticancer capacitySIM-A 9 microglial cell linenovel phytohormonesStrigolactone AnaloguePPAR γVitro Therapeutic Activitiesnovel anti-AD candidatesMultitarget Profilingrepresentative SLGR 24disease-modifying agents
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