Dataset: A 3x3 Evaluation Matrix of Biological Interactions of ARHGAP32, RGNEF (ARHGEF28), and TDP-43 in Neurodegenerative Disease found in PubMed Literature as of August 5, 2026 - PathMap Experiment #000098

Interactive Data Viewer: Read, View, and Print from Day 1 Use our fully interactive viewer to view, read, and print this research data right from Day 1: https://pathmap.org/viewer.php?id=98 Artificial General Intelligence LLC Claim Evaluated: A 3x3 Evaluation Matrix of Biological Interactions of ARHGAP32, RGNEF (ARHGEF28), and TDP-43 in Neurodegenerative Disease found in PubMed Literature as of August 5, 2026 This dataset contains the raw JSON execution trace, verified verbatim quotes, and MeSH-aligned logic gates generated by PathMap Studio's Veridical Enforcement engine. 🔍 Novel & Overlooked Insights RGNEF and TDP-43 interact within micronuclei, a novel mechanism for cytoplasmic aggregate formation in ALS. ARHGAP32, while a GAP protein, is itself a target of the very splicing dysregulation caused by nuclear TDP-43 depletion. RGNEF (ARHGEF28) has been identified as a candidate risk allele in population-based studies using item response theory. The C-terminal domain of KIF5A, often linked to ALS, also displays a basic isoelectric point, mirroring issues seen with certain mutated RGNEF variants. YAP serves as a potential modulator of TDP-43 condensates, showing that non-transcriptional pathways can alleviate proteinopathy. Lipid bilayers containing phosphatidylserine and cardiolipin can specifically accelerate TDP-43 CTD aggregation. TDP-43 is essential for skeletal muscle maintenance, translocating to mitochondria during maturation. Cryptic splicing events in genes like ARHGAP32 occur selectively in neurons already showing signs of TDP-43 pathology. 🧪 Extracted Custom Datapoints 📊 Suggested Experiments Investigate if ARHGAP32 splicing inhibition via ASOs rescues the mitochondrial bioenergetic defects observed in TDP-43 depleted models. Perform mass spectrometry to map the interaction interface between RGNEF and the RRM1/2 domains of TDP-43. 📊 Suggested Studies Longitudinal analysis of ARHGAP32 isoforms in iPSC-derived neurons during TDP-43 cytoplasmic mislocalization. Comparative study of RGNEF/ARHGEF28 variants across different ALS clinical subtypes to determine correlate pathology. 📊 Swansons Literature Based Discovery Candidates Inhibition of the Rho GTPase regulator EPS8 may prevent the cryptic splicing of ARHGAP32 that occurs downstream of TDP-43 cytoplasmic mislocalization. EPS8/RAC signaling hyperactivation promotes aggregation of TDP-43 (ID 40903652). ARHGAP32 is a major target of aberrant cryptic splicing in TDP-43 proteinopathy (ID 40478310). Rho GTPase signaling pathway homeostasis. Since EPS8 hyperactivation drives TDP-43 pathology and nuclear depletion is the prerequisite for ARHGAP32 cryptic splicing, normalizing the Rho signaling cascade via EPS8 inhibition should theoretically maintain TDP-43 nuclear localization, thereby preventing the downstream aberrant splicing of ARHGAP32. 📊 Contradictions Between Evidences Evidence regarding the protective vs. pathogenic role of FUS/TDP-43 aggregates is conflicting; while most sources describe them as causative of neurotoxicity (ID 41542389), yeast models suggest they may act as a sequestration reservoir that promotes longevity (ID 41614607). 📊 Repurposed Solutions Carboplatin, traditionally an anti-cancer agent, is repurposed to inhibit NF-κB in astrocytes, thereby mitigating TDP-43-induced neurotoxicity (ID 42134762). NU-9 is repurposed to stabilize the endolysosomal system, preventing accumulation of both SOD1 and TDP-43 aggregates (ID 40030015). Tags Attractor Table Extracted Keywords & Entities TDP-43 Proteinopathies, _gates_from_tdp-43_proteinopathies, RNA Splicing, _gates_to_rna_splicing, RGNEF (ARHGEF28), _gates_from_rgnef_(arhgef28), TDP-43, _gates_to_tdp-43 Run Your Own Analysis PathMap is a patent-pending universal AI workbench designed to eliminate LLM hallucinations in medical research. Generate your own autonomous discovery reports at PathMap.org.