Abstract:
:Deciphering the molecular mechanisms of amyloid pathology and glial cell-mediated neuroinflammation, offers a novel avenue for therapeutic intervention against neurodegeneration. Recent findings demonstrate a crucial link between activation of glycogen synthase kinase-3β (GSK-3β), amyloid deposition and a neuroinflammatory state. However, studies demonstrating the pharmacological effects of GSK-3β inhibition and the interlinked molecular mechanisms still remain elusive. The present study explores whether high fat-high fructose diet (HFFD)-induced neuropathological changes could be alleviated by indirubin-3'-monoxime (IMX), a GSK-3β inhibitor. Male Swiss albino mice (8 weeks old) were fed with normal pellet or HFFD for 60 days. HFFD mice were treated with IMX once daily for last 7 days of the experimental period. HFFD fed-mice had significant amyloid deposits in cerebral cortex and hippocampus, and protein expression analyses showed activation of GSK-3β, nuclear translocation of NF-κB p65 and upregulation of inflammatory (TNF-α, IL-6, COX-2), astrocytic (GFAP), glial surface (CD-68) and pro-apoptotic markers (Bax and caspase-3). IMX treatment promotes the inhibitory phosphorylation of GSK-3β at Ser9 and moreover, a marked reduction in the phosphorylation of IKK-β, which prevents translocation and activation of NF-κB. Protein expression studies in IMX-treated brain tissues positively correlate with the anti-neuroinflammatory effects of GSK-3β inhibition. Taken together, our results provide substantial evidence that IMX could potentially attenuate neuroinflammation in coordination with the master transcription factor-NF-κB.
journal_name
Int Immunopharmacoljournal_title
International immunopharmacologyauthors
Sathiya Priya C,Vidhya R,Kalpana K,Anuradha CVdoi
10.1016/j.intimp.2019.02.053subject
Has Abstractpub_date
2019-05-01 00:00:00pages
396-407eissn
1567-5769issn
1878-1705pii
S1567-5769(18)31272-4journal_volume
70pub_type
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journal_title:International immunopharmacology
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journal_title:International immunopharmacology
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journal_title:International immunopharmacology
pub_type: 杂志文章
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pub_type: 杂志文章,meta分析,评审
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journal_title:International immunopharmacology
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journal_title:International immunopharmacology
pub_type: 杂志文章,评审
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doi:10.1016/j.intimp.2008.02.011
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journal_title:International immunopharmacology
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journal_title:International immunopharmacology
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journal_title:International immunopharmacology
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pub_type: 杂志文章
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journal_title:International immunopharmacology
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