Abstract:
:Abnormal activation of the transcriptional factor STAT3 (signal transducer and activator of transcription 3) was recently associated with Alzheimer Disease (AD). STAT3 phosphorylation is critical for cytokine secretion linked to neuroinflammation. Moreover, STAT3 may act as a transcriptional regulator of BACE1 (β-APP cleaving enzyme-1), the key enzyme in amyloid β (Aβ) production. We have previously shown that neuroinflammation and increased brain BACE1 levels triggered by LPS-induced systemic inflammation in wild-type mice are associated with an enhanced STAT3 activation. Using this LPS model, the goal of this study was to investigate if a STAT3 inhibitor administration could be protective against neuroinflammation and abnormal BACE1 regulation. Our results show that intraperitoneal injection of Stattic, a molecule that selectively inhibits the activation of STAT3, decreases LPS-induced microglial activation in the hippocampus. In addition, STAT3 inhibition reduced brain levels of cytokines IL-6, IL-1β and TNF-α triggered by LPS systemic administration. A significant reduction of BACE1 levels was observed in the hippocampus of mice treated with LPS and Stattic compared to those exposed to LPS alone. Taking together, our results show that Stattic can protect hippocampus against two pathological hallmarks of AD, and pave the way for further explorations of the therapeutic potential of STAT3 inhibition in AD.
journal_name
Immunol Lettjournal_title
Immunology lettersauthors
Millot P,San C,Bennana E,Porte B,Vignal N,Hugon J,Paquet C,Hosten B,Mouton-Liger Fdoi
10.1016/j.imlet.2020.10.004subject
Has Abstractpub_date
2020-12-01 00:00:00pages
129-134eissn
0165-2478issn
1879-0542pii
S0165-2478(20)30400-4journal_volume
228pub_type
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journal_title:Immunology letters
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journal_title:Immunology letters
pub_type: 杂志文章
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journal_title:Immunology letters
pub_type: 杂志文章
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journal_title:Immunology letters
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doi:10.1016/0165-2478(85)90017-3
更新日期:1985-01-01 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/j.imlet.2006.12.005
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/0165-2478(91)90099-v
更新日期:1991-09-01 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
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journal_title:Immunology letters
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journal_title:Immunology letters
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/j.imlet.2009.11.002
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journal_title:Immunology letters
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更新日期:2014-09-01 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/j.imlet.2008.01.009
更新日期:2008-05-15 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/0165-2478(92)90193-r
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更新日期:1982-01-01 00:00:00
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journal_title:Immunology letters
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更新日期:1996-10-01 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
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更新日期:2000-04-03 00:00:00
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journal_title:Immunology letters
pub_type: 杂志文章
doi:10.1016/j.imlet.2018.09.010
更新日期:2018-11-01 00:00:00