ArticleBrain and behavior2017
The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease.
Article in Brain and behavior, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Redox reactivities of membrane-bound amyloid-β-Cu complexes and their targeting by metallothionein-3.Free radical biology & medicine · 2025Article
- Membrane insertion exacerbates the α-Synuclein-Cu(II) dopamine oxidase activity: Metallothionein-3 targets and silences all α-synuclein-Cu(II) complexes.Free radical biology & medicine · 2020Article
- Zinc transporters in Alzheimer's disease.Molecular brain · 2019Review
- Pro-Inflammatory Activation of A New Immortalized Human Microglia Cell Line.Brain sciences · 2019Article
- The human microglial HMC3 cell line: where do we stand? A systematic literature review.Journal of neuroinflammation · 2018Review
- Chemistry of mammalian metallothioneins and their interaction with amyloidogenic peptides and proteins.Chemical Society reviews · 2017Review
- The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease.Brain and behavior · 2017Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMetallothioneins (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.
objectivesThe 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.
methodsMTT 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.
resultsAll 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.
conclusionBenzothiazolone-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.
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