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.
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| NCT Number | NCT00674124 |
| Phase | Phase 1/2 |
| Status | Completed |
| Drug | Rapamycin (Sirolimus) |
| Dosage | 1-10 mg daily (various doses studied) |
| Patient Population | Adults with definite or probable ALS |
| Duration | 6-12 months |
| Sample Size | ~84 patients (24 in Phase 1, 60 in Phase 2) |
| Sponsor | Various academic medical centers |
| Associated Genes | 5-HT1AR, AADC, ABCA1, ABCA7, ABCB1, ABCD3, ABCG1, ACE |
| Therapeutic Agents | Antioxidants, Anti-oxidant Therapies, Antisense Oligonucleotides, Edavarone, Estradiol, Gene Therapy |
| SciDEX Hypotheses | 4 hypotheses |
| KG Connections | 8107 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 |
|---|---|---|---|
| Mitochondrial Function | inhibits | pathway | 1.00 |
| Mapk | inhibits | pathway | 1.00 |
| Mitochondrial Function | therapeutic_target | pathway | 1.00 |
| Nf-Κb | therapeutic_target | pathway | 1.00 |
| Mitophagy | therapeutic_target | pathway | 1.00 |
| Oxidative Phosphorylation | therapeutic_target | pathway | 1.00 |
| Oxidative Stress | inhibits | pathway | 1.00 |
| Phagocytosis | regulates | pathway | 1.00 |
| Toll-Like Receptor | activates | pathway | 1.00 |
| Mtor | therapeutic_target | pathway | 1.00 |
| Proteasome | inhibits | pathway | 1.00 |
| Mitophagy | activates | pathway | 1.00 |
| Mtor | inhibits | pathway | 1.00 |
| Glycolysis | therapeutic_target | pathway | 1.00 |
| Mitophagy | regulates | pathway | 1.00 |
| Necroptosis | activates | pathway | 1.00 |
| Glycolysis | activates | pathway | 1.00 |
| Ferroptosis | regulates | pathway | 1.00 |
| Apoptosis | inhibits | pathway | 1.00 |
| Longevity | associated_with | disease | 1.00 |
| Apoptosis | therapeutic_target | pathway | 1.00 |
| Mapk | therapeutic_target | pathway | 1.00 |
| Angiogenesis | activates | pathway | 1.00 |
| Mtor | regulates | pathway | 1.00 |
| Cholesterol | activates | pathway | 1.00 |
| Apoptosis | activates | pathway | 1.00 |
| Immune Response | activates | pathway | 1.00 |
| Oxidative Stress | activates | pathway | 1.00 |
| Epigenetic | therapeutic_target | pathway | 1.00 |
| Autophagy | therapeutic_target | pathway | 1.00 |
| Oxidative Stress | regulates | pathway | 1.00 |
| Wnt | therapeutic_target | pathway | 1.00 |
| Angiogenesis | therapeutic_target | pathway | 1.00 |
| Mitochondrial Function | regulates | pathway | 1.00 |
| Complement | activates | pathway | 1.00 |
| Blood-Brain Barrier | inhibits | pathway | 1.00 |
| Phagocytosis | activates | pathway | 1.00 |
| Lipid Metabolism | activates | pathway | 1.00 |
| Wnt | activates | pathway | 1.00 |
| Nf-Κb | activates | pathway | 1.00 |
| Ferroptosis | associated_with | pathway | 1.00 |
| Autophagy | interacts_with | pathway | 1.00 |
| Ferroptosis | inhibits | pathway | 1.00 |
| Complement | therapeutic_target | pathway | 1.00 |
| Autophagy | inhibits | pathway | 1.00 |
| Proteasome | activates | pathway | 1.00 |
| Blood-Brain Barrier | activates | pathway | 1.00 |
| Ubiquitin-Proteasome | activates | pathway | 1.00 |
| Lipid Metabolism | therapeutic_target | pathway | 1.00 |
| Angiogenesis | inhibits | pathway | 1.00 |
| Source | Relation | Type | Str |
|---|---|---|---|
| entities-microtubules | associated_with | wiki | 0.00 |
| entities-atp7b-gene | associated_with | wiki | 0.00 |
| entities-astrocytes | associated_with | wiki | 0.00 |
| entities-reactive-oxygen-species | associated_with | wiki | 0.00 |
| entities-histone-methylation | associated_with | wiki | 0.00 |
| entities-glp1-receptor | associated_with | wiki | 0.00 |
| entities-hepcidin | associated_with | wiki | 0.00 |
| entities-heat-shock-proteins | associated_with | wiki | 0.00 |
| entities-ros | associated_with | wiki | 0.00 |
| EXOSOMES | therapeutic_target | gene | 1.00 |
| AMYOTROPHIC LATERAL SCLEROSIS | activates | gene | 1.00 |
| PARKINSON'S DISEASE | interacts_with | gene | 1.00 |
| CGAS-STING | inhibits | gene | 1.00 |
| AGING | expressed_in | gene | 1.00 |
| DIABETES MELLITUS | therapeutic_target | gene | 1.00 |
| TAU | activates | gene | 1.00 |
| FERROPTOSIS | therapeutic_target | gene | 1.00 |
| OXIDATIVE STRESS | expressed_in | gene | 1.00 |
| NEURODEGENERATIVE DISEASES | expressed_in | gene | 1.00 |
| NEURODEGENERATION | inhibits | gene | 1.00 |
| AGING | regulates | gene | 1.00 |
| MIRNAS | regulates | gene | 1.00 |
| Inflammation | associated_with | disease | 1.00 |
| PIK3CA | therapeutic_target | gene | 1.00 |
| UBIQUITIN | therapeutic_target | gene | 1.00 |
| NF-ΚB | activates | gene | 1.00 |
| TNF-Α | inhibits | gene | 1.00 |
| INSULIN RESISTANCE | activates | gene | 1.00 |
| FOXO1 | activates | gene | 1.00 |
| IL-6 | inhibits | gene | 1.00 |
| IL-6 | activates | gene | 1.00 |
| DNA | regulates | gene | 1.00 |
| ALZHEIMER'S DISEASE | therapeutic_target | gene | 1.00 |
| DNA | therapeutic_target | gene | 1.00 |
| NF-ΚB | inhibits | gene | 1.00 |
| TNF-Α | activates | gene | 1.00 |
| CYTOKINES | inhibits | gene | 1.00 |
| AGING | therapeutic_target | gene | 1.00 |
| PARKINSON'S DISEASE | regulates | gene | 1.00 |
| MYC | therapeutic_target | gene | 1.00 |
| TP53 | inhibits | gene | 1.00 |
| ERK | inhibits | gene | 1.00 |
| MIRNAS | therapeutic_target | gene | 1.00 |
| P38 | therapeutic_target | gene | 1.00 |
| P38 | inhibits | gene | 1.00 |
| APP | regulates | gene | 1.00 |
| STAT3 | therapeutic_target | gene | 1.00 |
| AKT | activates | gene | 1.00 |
| OXIDATIVE STRESS | activates | gene | 1.00 |
| P38 | activates | gene | 1.00 |
Hypotheses where this entity is a therapeutic target
Scientific analyses that reference this entity
neurodegeneration | 2026-04-26 | 4 hypotheses Top: 0.776
neurodegeneration | 2026-04-25 | 7 hypotheses Top: 0.730
neurodegeneration | 2026-04-18 | 7 hypotheses Top: 0.620
neurodegeneration | 2026-04-18 | 0 hypotheses
neurodegeneration | 2026-04-18 | 4 hypotheses Top: 0.538
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| No experiments found | |||||||
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiqui [PMID:30966861] | ["Han X", "Sun S", "Sun Y", "Song Q", "Z | Autophagy | 2020 | 1 |
| Activation of stimulator of interferon genes (STING) and inhibition of vascular [PMID:41380972] | Wang Y, Hou Y, Han J, Zhang Z, Cheng Y e | J Biol Chem | 2026 | 0 |
| cGAS-STING signaling in Alzheimer's disease: Microglial mechanisms and therapeut [PMID:41481960] | Fazal F, Dar NJ, Ahamad S, Khan S, Bano | Mol Aspects Med | 2026 | 0 |
| Opportunities and challenges of targeting cGAS-STING in cancer. [PMID:41486397] | Lu C, Wang W, Fu YX | Nat Rev Cancer | 2026 | 0 |
| cGAS-STING activation in Parkinson's Disease: From mechanisms to Disease-Modifyi [PMID:41500413] | Solomon J, Mandal S, Aran KR | Gene | 2026 | 0 |
| STING-NF-κB signaling builds an influenza spillover barrier. [PMID:41747053] | Ye R, Wang S, Hu Y, Pan Y, Zheng W et al | Science | 2026 | 0 |
| The cGAS-STING signaling pathway: A central regulator and novel therapeutic targ [PMID:41765111] | Jiang H, Ji Y, Shang T, Qi L, Li Z et al | Biochem Pharmacol | 2026 | 0 |
| cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Tar [PMID:42016387] | Wang Y, Chen J, Feng W, Li N, Zhang X et | Drug Des Devel Ther | 2026 | 0 |
| Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438] | Hegdekar N, Sarkar C, Bustos S, Ritzel R | Autophagy | 2023 | 0 |
| Inflammasome assembly in neurodegenerative diseases. [PMID:37633753] | Singh J, Habean ML, Panicker N | Trends in neurosciences | 2023 | 0 |
| NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pat [PMID:34877938] | Li S, Sun Y, Song M, Song Y, Fang Y, Zha | JCI insight | 2021 | 0 |
| Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-de [PMID:30643298] | Melamed Z, López-Erauskin J, Baughn MW, | Nature neuroscience | 2019 | 0 |
| Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential thera [PMID:30127392] | Fujimori K, Ishikawa M, Otomo A, Atsuta | Nature medicine | 2018 | 0 |
| Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodeg [PMID:30381407] | Gordon R, Albornoz EA, Christie DC, Lang | Science translational medicine | 2018 | 0 |
Multi-agent debates referencing this entity
active · Rounds: 6 · Score: 0.75 · 2026-04-26
active · Rounds: 4 · Score: 0.65 · 2026-04-25
closed · Rounds: 4 · Score: 0.79 · 2026-04-22
closed · Rounds: 4 · Score: 0.69 · 2026-04-22
closed · Rounds: 4 · Score: 0.75 · 2026-04-22
closed · Rounds: 4 · Score: 0.73 · 2026-04-21
closed · Rounds: 4 · Score: 0.73 · 2026-04-21
closed · Rounds: 4 · Score: 0.70 · 2026-04-21
closed · Rounds: 4 · Score: 0.65 · 2026-04-21
closed · Rounds: 4 · Score: 0.77 · 2026-04-21
Hypotheses and analyses mentioning ALS in their description or question text
Score: 0.693 · ALS · 2026-04-26
Score: 0.682 · ALS · 2026-04-26
Score: 0.680 · Alzheimer disease · 2026-04-24
## Mechanistic Overview Hippocampal-Cortical Transcriptomic Divergence Reveals Accelerated Neurodegeneration-Like Signat
Score: 0.664 · neurodegeneration · 2026-04-13
**Molecular Mechanism and Rationale** The stathmin-2 splice switching therapeutic approach targets a fundamental pathom
Score: 0.648 · neurodegeneration · 2026-04-22
**Molecular Mechanism and Rationale** The OPTN/TBK1 phosphorylation cascade represents a critical quality control mecha
Score: 0.640 · neurodegeneration · 2026-04-22
## **Molecular Mechanism and Rationale** The cyclin-dependent kinase 5 (CDK5) represents a critical regulatory node in
Score: 0.621 · neurodegeneration · 2026-04-16
## Mechanistic Overview SYNJ1 Aggregation and Solubility Loss Impairs PI(4,5)P2 Cycling at Synaptic Terminals starts fro
Score: 0.620 · neurodegeneration · 2026-04-22
## Mechanistic Overview Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTD starts from the claim
Score: 0.610 · neuroscience · 2026-04-22
**Molecular Mechanism and Rationale** The apolipoprotein E4 (APOE4) isoform, present in approximately 25% of the popula
Score: 0.610 · neurodegeneration · 2026-04-22
## Mechanistic Overview ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberrant Condensate Sta
Score: 0.595 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The hypothesis centers on a novel mechanistic pathway linking amyloid-β42 (Aβ42)
Score: 0.590 · neurodegeneration · 2026-04-22
## Mechanistic Overview G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG-Targeting Interventions starts from
Score: 0.585 · neurodegeneration · 2026-04-22
**Molecular Mechanism and Rationale** The G3BP1 and G3BP2 proteins function as critical scaffolding molecules in the fo
Score: 0.584 · neurodegeneration · 2026-04-13
## Mechanistic Overview PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineurin→TFEB Cascade
Score: 0.562 · neurodegeneration · 2026-04-13
## Mechanistic Overview C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by PIKFYVE Inhibition via Lysosomal Ex