miR-126-5p Targets SP1 to Inhibit the Progression of Parkinson's Disease.

BACKGROUND: At present, symptomatic treatment may improve the life quality of Parkinson's disease (PD) patients to a certain extent but cannot completely cure PD. Therefore, it is urgent medical problem to be solved for improving the efficacy and safety of PD treatment. METHODS: SH-SY5Y and SK-N-SH cells were treated with 1-methyl-4-phenylpyridinium (MPP+) to establish PD model cells. miR-126-5p and specific protein-1 (SP1) expression levels were detected by quantitative Real-Time PCR (qRT-PCR). Western blot was applied to measure protein levels of SP1, Bax, and Bcl-2. The viabilities and apoptosis rates of treated cells were measured using cell counting kit-8 assay and flow cytometry analysis. Enzyme-linked immunosorbent assay was performed to measure TNF-α and IL-1ß releases. Interaction between miR-126-5p and SP1 was examined by dual-luciferase reporter assay. RESULTS: MPP+ treatment greatly downregulated miR-126-5p expression while upregulated SP1 expression in SH-SY5Y and SK-N-SH cells in a time- and does-dependent manner. Overexpression of miR-126-5p facilitated cell viability, while reduced cell apoptosis and inflammatory responses induced by MPP+ treatment. Moreover, SP1 was a target of miR-126-5p and could be negatively regulated by miR-126-5p. Overexpression of SP1 could reverse the effects of miR-126-5p on MPP+-administrated cells. CONCLUSION: Our results suggested that miR-126-5p attenuated the neurotoxicity induced by MPP+ in vitro through targeting SP1 (Graphical abstract), which further enhanced our understanding of the pathological mechanism of PD.

Molecular insights into the inhibitory mechanisms of gallate moiety on the Aß1-40 amyloid aggregation: A molecular dynamics simulation study.

Alzheimer's disease is the most common form of neurodegenerative disease and the formation of Aß amyloid aggregates has been widely demonstrated to be the principal cause of Alzheimer's disease. Our previous study and other studies suggested that the gallate moiety played an obligatory role in the inhibition process of naturally occurring polyphenols on Aß amyloid fibrils formation. However, the detailed mechanisms were still unknown. Thus, in the present study, the gallic acid (GA) was specially selected and the molecular recognition mechanisms between GA molecules and Aß1-40 monomer were examined and analyzed by molecular dynamics simulation. The in silico experiments revealed that GA significantly prevented the conformational changes of Aß1-40 monomer with no ß-sheet structure during the whole 100 ns. By analyzing the binding sites of GA molecules to Aß1-40 monomer, we found that both hydrophilic and hydrophobic amino acid residues were participated in the binding of GA molecules to Aß1-40 monomer. Moreover, results from the binding free energy analysis further demonstrated that the strength of polar interactions was significantly stronger than that of nonpolar interactions. We believed that our results could help to elucidate the underlying mechanisms of gallate moiety on the anti-amyloidogenic effects of polyphenols at the atomic level.

Molecular properties of water-unextractable proteoglycans from Hypsizygus marmoreus and their in vitro immunomodulatory activities.

Four proteoglycans were sequentially extracted from Hypsizygus marmoreus using 0.1 M NaOH (alkali-soluble proteoglycans [F1] and alkali-insoluble proteoglycans [F3]) and 0.1 M HCl (acid-soluble proteoglycans [F2] and acid-insoluble proteoglycans [F4]), and their structures and immunomodulatory activities were investigated. The proteoglycans were found to contain carbohydrates (19.8-82.4%) with various amounts of proteins (7.7-67.3%), and glucose was the major monosaccharide unit present, along with trace amounts of galactose. The molecular weights (Mw) and the radius of gyration (Rg) of these proteoglycans showed ranges of 16 × 10(4)-19,545 × 10(4) g/mol and 35-148 nm, respectively, showing significant variations in their molecular conformations. The backbones of F1 and F2 were mainly connected through a-(1→3), (1→4) and b-(1→6)-glycosidic linkages with some branches. The F1 and F2 proteoglycans significantly stimulated Raw264.7 cells to release nitric oxide (NO), prostaglandin E2 (PGE(2)) and various cytokines, such as IL-1ß, TNF-α and IL-6 by inducing their mRNA expressions.