Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about ALS: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disorder affecting upper and lower motor neurons. Approximately 10% of cases are familial, with mutations in genes including SOD1, C9orf72, TARDBP (TDP-43), and FUS. ALS pathology involves protein aggregation, RNA processing defects, mitochondrial dysfunction, and neuroinflammation.
| UNC13A | Variants in this gene modify disease progression and survival in ALS[@diekstra2012] |
| ATXN2 | Intermediate CAG repeats increase ALS risk approximately 2-fold[@soraru2013] |
| DAXX | Recent GWAS has identified this gene as a novel ALS risk factor[@van2023] |
| Loss of motor neurons | Progressive death ofcortical and spinal motor neurons with accompanying gliosis[@charcot1969] |
| Bunina bodies | Small, intracytoplasmic inclusions found in approximately 70% of cases[@bunina1962] |
| TDP-43 inclusions | Ubiquitinated inclusions containing phosphorylated TDP-43 in approximately 95% of ALS cases (both sporadic and most familial forms except SOD1)[@arai2006] |
| Dystrophic neurites | Abnormal neuronal processes surrounding inclusion bodies[@dickson2007] |
| Associated Genes | TDP43, CGAMP, C9ORF72, OPTN, SOD1, ALS_GENES, TREM2, UBQLN2 |
| Therapeutic Agents | sEVs, TUDCA, Trametinib, Antisense Oligonucleotides, Honokiol, Trehalose |
| KG Connections | 8483 knowledge graph edges |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
Knowledge base pages for this entity
graph TD
subgraph Pathology["Pathology"]
ALS["ALS"] -->|"associated with"| FTD["FTD"]
ALS["ALS"] -->|"associated with"| NEURON["NEURON"]
ALS["ALS"] -->|"associated with"| TAU["TAU"]
ALS["ALS"] -->|"associated with"| MICROGLIA["MICROGLIA"]
ALS["ALS"] -->|"associated with"| Als["Als"]
ALS["ALS"] -->|"associated with"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
ALS["ALS"] -->|"associated with"| Autophagy["Autophagy"]
C9ORF72["C9ORF72"] -->|"causes"| ALS["ALS"]
SOD1["SOD1"] -->|"causes"| ALS["ALS"]
OXIDATIVE_STRESS["OXIDATIVE STRESS"] -->|"associated with"| ALS["ALS"]
AXONAL_TRANSPORT_DEFECTS["AXONAL TRANSPORT DEFECTS"] -->|"associated with"| ALS["ALS"]
AMYOTROPHIC_LATERAL_SCLEROSIS["AMYOTROPHIC LATERAL SCLEROSIS"] -->|"associated with"| ALS["ALS"]
end
subgraph Signaling["Signaling"]
ALS["ALS"] -->|"activates"| Neurodegeneration["Neurodegeneration"]
ALS["ALS"] -->|"activates"| Als_1["Als"]
end
subgraph Therapeutic["Therapeutic"]
NEURODEGENERATIVE_DISEASES["NEURODEGENERATIVE DISEASES"] -->|"therapeutic target"| ALS["ALS"]
end
style ALS fill:#ef5350,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
style FTD fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style NEURON fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style TAU fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style MICROGLIA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Amyotrophic_Lateral_Sclerosis fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Neurodegeneration fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Als_1 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style Autophagy fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style C9ORF72 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style SOD1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style OXIDATIVE_STRESS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style AXONAL_TRANSPORT_DEFECTS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style AMYOTROPHIC_LATERAL_SCLEROSIS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
style NEURODEGENERATIVE_DISEASES fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0| Target | Relation | Type | Str |
|---|---|---|---|
| FTD | associated_with | disease | 1.00 |
| NEURON | associated_with | gene | 1.00 |
| TAU | associated_with | gene | 1.00 |
| MICROGLIA | associated_with | gene | 1.00 |
| Als | associated_with | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | associated_with | disease | 1.00 |
| Neurodegeneration | activates | disease | 1.00 |
| Als | activates | disease | 1.00 |
| Autophagy | associated_with | pathway | 1.00 |
| Dementia | associated_with | disease | 1.00 |
| Inflammation | activates | disease | 1.00 |
| Als | inhibits | disease | 1.00 |
| Als | therapeutic_target | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | therapeutic_target | disease | 1.00 |
| Als | regulates | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | biomarker_for | disease | 1.00 |
| Alzheimer | associated_with | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | activates | disease | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | regulates | gene | 1.00 |
| Amyotrophic Lateral Sclerosis | regulates | disease | 1.00 |
| Parkinson | associated_with | disease | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | associated_with | gene | 1.00 |
| MOTOR NEURONS | associated_with | gene | 1.00 |
| AUTOPHAGY | associated_with | gene | 1.00 |
| SOD1 | associated_with | gene | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | therapeutic_target | gene | 1.00 |
| Inflammation | associated_with | disease | 1.00 |
| Amyotrophic Lateral Sclerosis | interacts_with | disease | 1.00 |
| Aging | therapeutic_target | disease | 1.00 |
| NEURODEGENERATION | activates | gene | 1.00 |
| Neurodegeneration | therapeutic_target | disease | 1.00 |
| Als | contributes_to | disease | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | interacts_with | gene | 1.00 |
| MOTOR NEURONS | activates | gene | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | activates | gene | 1.00 |
| NEURODEGENERATION | associated_with | gene | 1.00 |
| Neurodegeneration | associated_with | disease | 1.00 |
| DEMENTIA | interacts_with | gene | 1.00 |
| HUNTINGTON | associated_with | gene | 1.00 |
| TARDBP | associated_with | gene | 1.00 |
| GENES | activates | gene | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | causes | gene | 1.00 |
| Amyotrophic Lateral Sclerosis | causes | disease | 1.00 |
| PARKINSON'S DISEASE | associated_with | gene | 1.00 |
| HUNTINGTON'S DISEASE | associated_with | gene | 1.00 |
| DEMENTIA | activates | gene | 1.00 |
| DEMENTIA | associated_with | gene | 1.00 |
| DEMENTIA | causes | gene | 1.00 |
| Dementia | causes | disease | 1.00 |
| NEUROINFLAMMATION | associated_with | gene | 1.00 |
| Source | Relation | Type | Str |
|---|---|---|---|
| C9ORF72 | causes | gene | 1.00 |
| SOD1 | causes | gene | 1.00 |
| OXIDATIVE STRESS | associated_with | gene | 1.00 |
| AXONAL TRANSPORT DEFECTS | associated_with | gene | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | associated_with | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | therapeutic_target | gene | 1.00 |
| NEURODEGENERATION | activates | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | associated_with | gene | 1.00 |
| C9ORF72 | associated_with | gene | 1.00 |
| PARKINSON'S DISEASE | associated_with | gene | 1.00 |
| NEURODEGENERATION | therapeutic_target | gene | 1.00 |
| PARKINSON | associated_with | gene | 1.00 |
| ALZHEIMER | associated_with | gene | 1.00 |
| NEURODEGENERATION | associated_with | gene | 1.00 |
| MIRO1 | downregulated_in | protein | 1.00 |
| SQSTM1 | associated_with | gene | 1.00 |
| INFLAMMATION | activates | gene | 1.00 |
| TDP43 | associated_with | protein | 0.97 |
| ALZHEIMER | activates | gene | 0.95 |
| PARKINSON | activates | gene | 0.95 |
| HUNTINGTON | activates | gene | 0.95 |
| NEURODEGENERATION | causes | gene | 0.95 |
| PIKFYVE | targets | gene | 0.95 |
| TDP43 | implicated_in | entity | 0.95 |
| PIKFYVE | therapeutic_target | entity | 0.95 |
| TDP43 | biomarker_for | entity | 0.95 |
| MICROGLIA | implicated_in | entity | 0.95 |
| STING | associated_with | protein | 0.95 |
| NfL | biomarker_for | biomarker | 0.95 |
| OPTN | risk_factor_for | gene | 0.95 |
| TARDBP | involved_in | protein | 0.95 |
| FUS | involved_in | protein | 0.95 |
| AGING | risk_factor_for | process | 0.95 |
| Inflammasome | contributes_to | pathway | 0.95 |
| NEAT1 | upregulates | gene | 0.95 |
| NEUROINFLAMMATION | involved_in | process | 0.95 |
| Parthanatos | involved_in | pathway | 0.95 |
| Stem Cell Therapies | treats | process | 0.95 |
| Motor Neuron Degeneration | contributes_to | phenotype | 0.95 |
| Riluzole | treats | drug | 0.95 |
| Edavarone | treats | drug | 0.95 |
| TARDBP | biomarker_for | protein | 0.95 |
| Nfl | biomarker_for | biomarker | 0.95 |
| FOXO1 | mediates | gene | 0.95 |
| ATXN2 | risk_factor_for | gene | 0.95 |
| Neuromuscular Junction Disassembly | contributes_to | process | 0.95 |
| Tofersen | treats | drug | 0.95 |
| Cryptic Hdgfl2 | biomarker_for | biomarker | 0.93 |
| OPTN | associated_with | gene | 0.92 |
| Pi3K-Akt | involved_in | pathway | 0.92 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| Stathmin-2 Splice Switching to Prevent Axonal Degeneration A | 0.664 | neurodegeneration | RNA binding protein dysregulation across |
| Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 | 0.601 | neurodegeneration | What are the mechanisms by which gut mic |
| PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5 | 0.559 | neurodegeneration | How does PIKFYVE inhibition activate unc |
| C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by | 0.537 | neurodegeneration | How does PIKFYVE inhibition activate unc |
Scientific analyses that reference this entity
neurodevelopment | 2026-04-15 | 1 hypotheses Top: 0.576
neurodegeneration | 2026-04-15 | 2 hypotheses Top: 0.455
neurodegeneration | 2026-04-14 | 1 hypotheses Top: 0.548
neurodegeneration | 2026-04-14 | 1 hypotheses Top: 0.604
neurodegeneration | 2026-04-14 | 1 hypotheses Top: 0.606
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| No papers found | ||||