Caffeic acid phenethyl ester inhibits mGluR5-Fyn signaling to alleviate neuroinflammation and pathological changes in Alzheimer disease
10.3969/j.issn.1000-4718.2025.05.001
- VernacularTitle:咖啡酸苯乙酯通过抑制mGluR5-Fyn表达减轻AD的神经炎症及病理改变
- Author:
Yuxiang LIU
1
;
Yani HE
1
;
Xueying LIN
1
;
Sihan PENG
1
;
Shuyi LI
1
;
Keke ZHANG
1
;
Wei WEI
1
Author Information
1. 暨南大学基础医学与公共卫生学院病理生理学系,国家中医药管理局病理生理学实验室,广东 广州 510632
- Publication Type:Journal Article
- Keywords:
caffeic acid phenethyl ester;
Alzheimer disease;
metabotropic glutamate receptor 5;
tyrosine ki-nase Fyn;
neuroinflammation
- From:
Chinese Journal of Pathophysiology
2025;41(5):833-842
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.
