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A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
1KM Medicine Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-Daero, Yuseong-Gu, Daejeon 305811, Republic of Korea.
Abstract:
Amyotrophic lateral sclerosis (ALS) is caused by selective the loss of spinal motor neurons by multifactorial pathological mechanisms and results in muscle atrophy. Incidence rates of ALS are increasing over time, but there are no effective treatments at present due to limitations on approved therapies (riluzole and edaravone). Therefore, this study investigated whether combined treatment with Bojungikgi-tang and riluzole could act synergistically in transactive response DNA-binding protein 43 (TDP-43) stress granule cells. To examine the effect of combined treatment on oxidative stress-induced cell death, the CCK8 assay was performed for the detection of cell viability. The expression of oxidative stress-induced proteins was determined by Western blot. Quantification of sodium arsenite-induced reactive oxygen species (ROS) was measured in TDP-43 stress granular cells using 2,7-diacetyl dichlorofluorescein diacetate. To investigate the effect of combined treatment on TDP-43 aggregation, immunofluorescence and immunoblotting were performed in TDP-43 stress granular cells. This combined treatment alleviated oxidative stress-induced cell death by increasing the expression levels of antioxidation proteins, such as heme oxygenase-1 and B cell lymphoma-2-associated X protein. Furthermore, it reduced oxidative stress-induced TDP-43 aggregates and lowered the levels of autophagy-related proteins, including p62, light chain 3b, and ATG8, in TDP-43-expressing cells. Our results suggest that this combined treatment could be helpful for autophagy regulation in other neurodegenerative diseases.
Insights
This study shows that combining Bojungikgi-tang with riluzole may help treat amyotrophic lateral sclerosis (ALS). The treatment reduced cell death and protein aggregation, offering potential for neurodegenerative disease therapy.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Amyotrophic lateral sclerosis (ALS) involves motor neuron loss and muscle atrophy, with increasing incidence and limited effective treatments.
- Current approved therapies for ALS, riluzole and edaravone, have limitations, necessitating novel therapeutic strategies.
- Transactive response DNA-binding protein 43 (TDP-43) aggregation and oxidative stress are key pathological mechanisms in ALS.
Purpose of the Study:
- To investigate the synergistic effects of combined Bojungikgi-tang and riluzole treatment on TDP-43 stress granule cells.
- To evaluate the impact of this combined treatment on oxidative stress-induced cell death and TDP-43 aggregation.
- To explore the potential of this combination therapy for regulating autophagy in neurodegenerative diseases.
Main Methods:
- Cell viability was assessed using the CCK8 assay.
- Protein expression of oxidative stress markers and TDP-43 was analyzed via Western blot.
- Reactive oxygen species (ROS) levels were quantified using 2,7-diacetyl dichlorofluorescein diacetate.
- TDP-43 aggregation was examined using immunofluorescence and immunoblotting.
Main Results:
- The combined treatment significantly alleviated oxidative stress-induced cell death.
- Expression of antioxidant proteins, including heme oxygenase-1 and BCL-2-associated X protein, was increased.
- The treatment reduced TDP-43 aggregation and decreased levels of autophagy-related proteins (p62, LC3B, ATG8).
Conclusions:
- Combined Bojungikgi-tang and riluzole treatment demonstrates a protective effect against oxidative stress and TDP-43 aggregation in motor neuron models.
- This synergistic approach shows promise for managing ALS pathology by modulating oxidative stress and protein aggregation.
- The findings suggest potential therapeutic benefits for autophagy regulation in neurodegenerative diseases beyond ALS.
