From knowledge landscapes to network mechanisms: charting regulated cell death pathways in ALS

Objective: To map the research landscape linking amyotrophic lateral sclerosis (ALS) with regulated cell death (RCD) and to integrate bibliometric trends with bioinformatics evidence to identify convergent mechanisms and actionable targets. Methods: Web of Science Core Collection, PubMed, and Scopus were searched for 2005-2024 (English; Article/Review). After merging and de-duplication, 6,272 records were analyzed using CiteSpace, VOSviewer, and bibliometrix to evaluate publication trends, collaboration, co-citation structure, and keyword evolution. In parallel, ALS-related genes were intersected with apoptosis-, ferroptosis-, and pyroptosis-associated gene sets. Shared targets were used to construct PPI networks, identify core modules and hub genes, and perform GO/KEGG enrichment analyses. Results: Publications and citations increased steadily with a clear rise after 2015. The field is anchored by the USA and shows rapidly growing contributions from Asia and Europe. Keyword evolution indicates a shift from "oxidative stress/apoptosis" toward multi-pathway RCD, with prominent recent bursts in ferroptosis, pyroptosis, necroptosis, and autophagy/mitophagy, alongside persistent themes in motor-neuron degeneration, mitochondria, and neuro-inflammation. Bio-informatics results showed substantial genetic overlap between ALS and RCD modalities. Hub-gene analysis highlighted TP53, AKT1, STAT3, MYC, RELA, EP300, CREBBP, JUN, HSP90AA1, and MAPK3 as central nodes. Enrichment analyses implicated FoxO, HIF-1, and lipid-related pathways, and GO terms related to chemical/oxidative stress responses and autophagy regulation. Conclusion: ALS-cell death research is consolidating around interconnected RCD programs. Integrated bibliometric and bioinformatics evidence supports an immunometabolic convergence involving ferroptosis-inflammation-autophagy signaling, providing a focused set of candidate pathways and hub targets for mechanistic validation and translation.