Related Experiment Video
Updated: Jun 22, 2026
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models
Makiko Yamashita1, Takashi Nonaka, Tetsuaki Arai
1Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Reearch, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Abstract:
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are major neurodegenerative diseases with TDP-43 pathology. Here we investigated the effects of methylene blue (MB) and dimebon, two compounds that have been reported to be beneficial in phase II clinical trials of Alzheimer's disease (AD), on the formation of TDP-43 aggregates in SH-SY5Y cells. Following treatment with 0.05 microM MB or 5 microM dimebon, the number of TDP-43 aggregates was reduced by 50% and 45%, respectively. The combined use of MB and dimebon resulted in a 80% reduction in the number. These findings were confirmed by immunoblot analysis. The results indicate that MB and dimebon may be useful for the treatment of ALS, FTLD-U and other TDP-43 proteinopathies.
Insights
Methylene blue (MB) and dimebon significantly reduced TDP-43 aggregates in cells, hallmarks of neurodegenerative diseases like ALS and FTLD-U. Combined treatment showed an 80% reduction, suggesting therapeutic potential for TDP-43 proteinopathies.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are characterized by TDP-43 protein aggregation.
- TDP-43 pathology is a common feature in major neurodegenerative diseases.
Purpose of the Study:
- To investigate the efficacy of methylene blue (MB) and dimebon in reducing TDP-43 aggregate formation.
- To evaluate the combined effect of MB and dimebon on TDP-43 aggregation.
Main Methods:
- SH-SY5Y cells were treated with varying concentrations of MB and dimebon.
- TDP-43 aggregate formation was quantified following compound treatment.
- Immunoblot analysis was used to confirm the observed effects.
Main Results:
- Methylene blue (MB) treatment reduced TDP-43 aggregates by 50%.
- Dimebon treatment reduced TDP-43 aggregates by 45%.
- Combined MB and dimebon treatment resulted in an 80% reduction in TDP-43 aggregates.
Conclusions:
- MB and dimebon demonstrate significant potential in mitigating TDP-43 aggregation.
- These compounds may offer a therapeutic strategy for ALS, FTLD-U, and other TDP-43 proteinopathies.
More Related Videos
04:56Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
06:27Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018