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Published on: October 6, 2015
The Involvement of RAGE and Its Ligands during Progression of ALS in SOD1 G93A Transgenic Mice
Natalia Nowicka1, Kamila Szymańska1, Judyta Juranek1
1Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
Abstract:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive degeneration of upper and lower motor neurons that causes paralysis and muscle atrophy. The pathogenesis of the disease is still not elucidated. Receptor for Advanced Glycation End Product (RAGE) is a major component of the innate immune system and has implications in ALS pathogenesis. Multiple studies suggest the role of RAGE and its ligands in ALS. RAGE and its ligands are overexpressed in human and murine ALS motor neurons, astrocytes, and microglia. Here, we demonstrated the expression of RAGE and its ligands during the progression of the disease in the transgenic SOD1 G93A mouse lumbar spinal cord. We observed the highest expression of HMGB1 and S100b proteins at ALS onset. Our results highlight the potential role of RAGE and its ligands in ALS pathogenesis and suggest that some of the RAGE ligands might be used as biomarkers in early ALS diagnosis and potentially be useful in targeted therapeutic interventions at the early stage of this devastating disease.
Insights
Receptor for Advanced Glycation End Product (RAGE) and its ligands are implicated in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Their elevated expression in early disease stages suggests potential as biomarkers for diagnosis and therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder impacting motor neurons.
- The precise mechanisms underlying ALS pathogenesis remain incompletely understood.
- Receptor for Advanced Glycation End Product (RAGE) is linked to innate immunity and implicated in ALS.
Purpose of the Study:
- To investigate the expression patterns of RAGE and its ligands during ALS progression.
- To explore the potential role of RAGE signaling in the pathogenesis of ALS.
- To identify potential early diagnostic biomarkers and therapeutic targets for ALS.
Main Methods:
- Utilized a transgenic SOD1 G93A mouse model of ALS.
- Analyzed the expression of RAGE and its ligands in the lumbar spinal cord.
- Quantified protein levels of HMGB1 and S100b at different disease stages.
Main Results:
- RAGE and its ligands were found to be overexpressed in ALS models.
- Highest expression of HMGB1 and S100b proteins was observed at the onset of ALS.
- Demonstrated the dynamic expression of RAGE and ligands throughout disease progression.
Conclusions:
- RAGE and its ligands play a significant role in ALS pathogenesis.
- HMGB1 and S100b may serve as potential biomarkers for early ALS detection.
- Targeting RAGE pathways could offer novel therapeutic strategies for early-stage ALS.
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