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From knowledge landscapes to network mechanisms: charting regulated cell death pathways in ALS
Jingxuan Zhang1, Zilin Zhao2, Tianyue Xiang2
1First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China.
Frontiers in Aging Neuroscience
|February 16, 2026
Summary
Research on amyotrophic lateral sclerosis (ALS) and regulated cell death (RCD) is expanding, revealing interconnected pathways. Bioinformatics and bibliometrics pinpoint immunometabolic signaling as a key convergence, highlighting ferroptosis, inflammation, and autophagy for potential therapeutic targets.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Regulated cell death (RCD) pathways are increasingly implicated in ALS pathogenesis.
- Understanding the interplay between ALS and RCD is crucial for identifying therapeutic targets.
Purpose of the Study:
- To map the research landscape of amyotrophic lateral sclerosis (ALS) and regulated cell death (RCD).
- To integrate bibliometric trends with bioinformatics data to identify convergent mechanisms and actionable targets in ALS-RCD research.
Main Methods:
- Bibliometric analysis of 6,272 publications (2005-2024) using CiteSpace, VOSviewer, and bibliometrix.
- Bioinformatics analysis intersecting ALS-related genes with apoptosis, ferroptosis, and pyroptosis gene sets.
- Construction of protein-protein interaction (PPI) networks, identification of core modules, hub genes, and enrichment analyses (GO/KEGG).
Main Results:
- Publication and citation rates for ALS-RCD research show a significant increase after 2015, with growing global contributions.
- Keyword evolution indicates a shift towards multi-pathway RCD, including ferroptosis, pyroptosis, and autophagy, alongside persistent ALS themes.
- Bioinformatics revealed genetic overlap between ALS and RCD, identifying TP53, AKT1, STAT3, and MYC as key hub genes, and implicating lipid, FoxO, and HIF-1 pathways.
Conclusions:
- ALS and RCD research is converging on interconnected cell death programs.
- Integrated evidence supports an immunometabolic convergence involving ferroptosis, inflammation, and autophagy signaling in ALS.
- This study provides a focused set of candidate pathways and hub targets for further mechanistic validation and therapeutic translation.
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