Related Experiment Video
Updated: Mar 11, 2026
Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function
Published on: January 22, 2017
Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease
C M Lopes-Ramos1, T C Pereira2, D B Dogini1
1Departamento de Genética Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Insights
Lithium carbonate and coenzyme Q10 show promise in reducing cell death in Machado-Joseph disease (MJD/SCA3) models. These treatments increased cell viability by decreasing apoptosis and altering ATX3 protein aggregation.
Area of Science:
- Neurodegenerative Disorders
- Molecular Biology
- Pharmacology
Background:
- Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a prevalent autosomal dominant neurodegenerative disorder.
- It is caused by the expansion of the polyglutamine domain in the ataxin-3 (ATX3) protein, leading to protein misfolding, aggregation, neuronal dysfunction, and cell death.
- Currently, no effective treatments exist for MJD/SCA3.
Purpose of the Study:
- To investigate the potential therapeutic effects of lithium carbonate and coenzyme Q10 on cell death induced by expanded ATX3 in a cellular model of MJD/SCA3.
- To evaluate the impact of these compounds on cell viability, apoptosis, and the aggregation state of the expanded ATX3 protein.
Main Methods:
- Cell viability was assessed using the MTT assay.
- Apoptosis was quantified via flow cytometry using annexin V-FITC and propidium iodide staining.
- Changes in the monomer/aggregate ratio of expanded ATX3 (Q84) were analyzed after treatment.
Main Results:
- Treatment with lithium carbonate and coenzyme Q10 significantly increased the viability of cells expressing expanded ATX3 (Q84).
- This increase in cell viability was attributed to a significant reduction in the proportion of apoptotic cells.
- A significant shift in the ATX3 monomer/aggregate ratio was observed, favoring the monomeric form and reducing aggregates.
Conclusions:
- Lithium carbonate and coenzyme Q10 demonstrate potential as therapeutic agents for MJD/SCA3 by mitigating cell death associated with expanded ATX3.
- The observed reduction in apoptosis and altered protein aggregation suggest a promising mechanism of action.
- Given the established safety profiles of both drugs, they warrant further investigation in in vivo therapeutic trials for MJD/SCA3.
Abstract:
Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...