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- Title
The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease.
- Authors
Roy, Sudeep; Gumulec, Jaromir; Kumar, Akhil; Raudenska, Martina; Baig, Mohd Hassan; Polanska, Hana; Balvan, Jan; Gupta, Mansi; Babula, Petr; Odstrčilík, Jan; Choi, Inho; Provaznik, Ivo; Masarik, Michal
- Abstract
Introduction Metallothioneins ( MTs) are a class of ubiquitously occurring low-molecular-weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. MT-3 exhibits neuro-inhibitory activity. The possibility to enhance the expression of MT-3 or protect it from degradation is an attractive therapeutic target, because low levels of MT-3 were found in brains of Alzheimer's disease ( AD) patients. Objectives The primary objective of this study was to test an enhancement of MT-3 cellular concentration after MT-3 binding treatment, which could prevent MT-3 degradation. Methods MTT assay, flow-cytometry, fluorescence microscopy, quantitative real-time polymerase chain reaction, and immunodetection of MT3 were used for analysis of effect of STOCK1N-26544, STOCK1N-26929, and STOCK1N-72593 on immortalized human microglia- SV40 cell line. Results All three tested compounds enhanced concentration of MT-3 protein in cells and surprisingly also mRNA concentration. IC50 values of tested molecules exceeded about ten times the concentration that was needed for induction of MT-3 expression. The tested compound Benzothiazolone-2 enhanced apoptosis and necrosis, but it was not of severe effect. About 80% of cells were still viable. There was no serious ROS-generation and no severe decrease in mitochondria numbers or stress induced endoplasmic reticulum changes after test treatments. The selected compound showed stable hydrophobic and electrostatic interaction during MT-3 ligand interaction. Conclusion Benzothiazolone-2 compounds significantly enhanced MT-3 protein and mRNA levels. The compounds can be looked upon as one of the probable lead compounds for future drug designing experiments in the treatment of Alzheimer's disease.
- Subjects
METALLOTHIONEIN; PROTEIN expression; ALZHEIMER'S disease; METAL clusters; POLYMERASE chain reaction
- Publication
Brain & Behavior, 2017, Vol 7, Issue 9, pn/a
- ISSN
2162-3279
- Publication type
Article
- DOI
10.1002/brb3.799