Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-
10.1016/j.apsb.2021.03.020
- Author:
Zhe ZHAO
1
;
Fangyuan LI
1
;
Jingwen NING
1
;
Ran PENG
1
;
Junmei SHANG
1
;
Hui LIU
1
;
Meiyu SHANG
1
;
Xiu-Qi BAO
1
;
Dan ZHANG
1
Author Information
1. State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
ANOSIM, adonis and analysis of similarity;
BBB, blood–brain barrier;
CFU, colony-forming units;
CMC-Na, sodium carboxymethyl cellulose;
CNS, central nerve system;
ELISA, enzyme-linked immunosorbent assay;
FD4, FITC-dextran (MW: 4 kDa);
FITC, fluorescein isothiocyanate;
FLZ;
GFAP, glial fibrillary acidic protein;
GI, gastrointestinal;
Gastrointestinal dysfunction;
Hp, Helicobacter pylori;
IL-1β, interleukin-1β;
IL-6, interleukin-6;
Iba-1, ionized calcium-binding adapter molecule 1;
KEGG, Kyoto Encyclopedia of Genes and Genomes;
LBP, lipopolysaccharide binding protein;
LDA, linear discriminant analysis;
LPS, lipopolysaccharide;
MLNs, mesenteric lymph nodes;
Microbiota–gut–brain axis;
Neuroinflammation;
OTU, operational taxonomic unit;
PBS, phosphate-buffered saline;
PCoA, principal coordinate analysis;
PD, Parkinson's disease;
Parkinson's disease;
Rotenone mouse model;
SD, standard deviation;
SN, substantia nigra;
Systemic inflammation;
TEM, transmission electron microscopy;
TH, tyrosine hydroxylase;
TLR4, toll-like receptor 4;
TLR4/MyD88/NF-κB pathway;
TNF-α, tumor necrosis factor-α;
qPCR, quantitative polymerase chain reaction assay;
α-Syn, α-synuclein
- From:
Acta Pharmaceutica Sinica B
2021;11(9):2859-2879
- CountryChina
- Language:English
-
Abstract:
Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ
