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Minerva Medica 2020 Mar 20

DOI: 10.23736/S0026-4806.20.06463-0


language: English

Study on the mechanism of curcumin to reduce the inflammatory response of temporal lobe in Alzheimer's disease by regulating miR-146a

Jingfeng GONG 1 , Derong SUN 2

1 Department of Neurology (I), The Fourth Hospital of Daqing, Daqing, P.R. China; 2 General Department, North Banch of The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China


BACKGROUND: To explore the potential mechanism of curcumin in the treatment of Alzheimer's disease and clarify the role of miR-146a in the neuroinflammatory response to Alzheimer's disease.
METHODS: Clinical case study: 20 AD patients and 20 age-gender matched non-inflammatory and non-dementia patients in the department of neurology of our hospital were included, peripheral venous blood and cerebrospinal fluid were collected, and mir-146a levels in peripheral blood and cerebrospinal fluid were detected by real-time fluorescence quantitative PCR. Animal experimental study group: There were 3 groups, including APP/PS1 mice control group, APP/PS1 mice low-dose curcumin treatment group, and C57BL/6J mice wild-type (WT) control group, with 10 mice in each group. mir-146a levels in mice brain tissue were detected by quantitative real-time PCR. Aβ, APP, complement factor H (CFH) and M1 microglia labeled IL-1 β and iNOS in temporal lobe tissues of mice were detected by using Westernblot method.
RESULTS: The plasma miRNA-146a level in AD group was 39.10 ±12.97 fmol/L, and that in control group was 60.54 ±13.16 fmol/L. The plasma miRNA-146a level in AD group was significantly lower than that in control group. The level of miRNA-146a in cerebrospinal fluid of AD group (25.16 ± 5.16 fmol/L) was significantly higher than that of control group (11.35 ±3.58 fmol/L). After treatment with low dose curcumin, the level of miRNA-146a in APP/PS1 mice decreased significantly, and the expression of A β and APP/PS1 in temporal lobe of mice detected by Western blot decreased significantly, the levels of IL-1 β and iNOS protein decreased significantly, and the protein of CFH increased signifanctly.
CONCLUSIONS: miRNA-146a can be used as one of the potential biomarkers of AD. Low dose curcumin can significantly reduce the level of neuropro-inflammatory miR-146A, up-regulate the expression of CFH protein, inhibit the phenotype of M1 microglia, and play a role in the treatment of AD by promoting the phagocytosis and clearance mechanism of A β.

KEY WORDS: Curcumin; Alzheimer's disease; miRNA-146a; M1 microglia

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