disease

ALS

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

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.

18743Connections

23Hypotheses

30Analyses

50Outgoing

50Incoming

0Experiments

20Debates

Summary

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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Disease Info

Associated Genes	5-HT1AR, AADC, ABCA1, ABCA7, ABCB1, ABCD3, ABCG1, ACE
Therapeutic Agents	Antioxidants, Anti-oxidant Therapies, Antisense Oligonucleotides, Edavarone, Estradiol, Gene Therapy
KG Connections	8772 knowledge graph edges
Databases	OMIM Orphanet ClinicalTrials PubMed

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

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

Outgoing (5367)

Target	Relation	Type	Str
Parkinson	associated_with	disease	1.00
SOD1	associated_with	gene	1.00
AMYOTROPHIC LATERAL SCLEROSIS	regulates	gene	1.00
Amyotrophic Lateral Sclerosis	regulates	disease	1.00
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	1.00
AUTOPHAGY	associated_with	gene	1.00
Als	regulates	disease	1.00
Necroptosis	therapeutic_target	pathway	1.00
Oxidative Stress	expressed_in	pathway	1.00
Lipid Metabolism	associated_with	pathway	1.00
Alzheimer	associated_with	disease	1.00
Amyotrophic Lateral Sclerosis	therapeutic_target	disease	1.00
Autophagy	regulates	pathway	1.00
MOTOR NEURONS	associated_with	gene	1.00
Chaperone	therapeutic_target	pathway	1.00
Lysosomal Degradation	therapeutic_target	pathway	1.00
Mapk	activates	pathway	1.00
Inflammasome	therapeutic_target	pathway	1.00
Proteasome	regulates	pathway	1.00
Angiogenesis	inhibits	pathway	1.00
Oxidative Phosphorylation	regulates	pathway	1.00
Ubiquitin-Proteasome	regulates	pathway	1.00
Oxidative Stress	contributes_to	pathway	1.00
Amyotrophic Lateral Sclerosis	biomarker_for	disease	1.00
Obesity	associated_with	disease	1.00
Proteasome	inhibits	pathway	1.00
Apoptosis	regulates	pathway	1.00
Insulin Signaling	activates	pathway	1.00
Senescence	associated_with	disease	1.00
Cholesterol	associated_with	pathway	1.00
Mapk	inhibits	pathway	1.00
Epigenetic	inhibits	pathway	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
Carcinoma	associated_with	disease	1.00
Er Stress	activates	pathway	1.00
Inflammasome	activates	pathway	1.00
Pyroptosis	activates	pathway	1.00
Lipid Metabolism	inhibits	pathway	1.00
Immune Response	regulates	pathway	1.00
Tgf-Β	therapeutic_target	pathway	1.00
Apoptosis	inhibits	pathway	1.00
Dna Methylation	regulates	pathway	1.00
Mtor	regulates	pathway	1.00
Synaptic Plasticity	activates	pathway	1.00
Synaptic Plasticity	regulates	pathway	1.00
Immune Response	inhibits	pathway	1.00
Complement	regulates	pathway	1.00
Nf-Κb	inhibits	pathway	1.00
Glycolysis	regulates	pathway	1.00
AMYOTROPHIC LATERAL SCLEROSIS	therapeutic_target	gene	1.00

Incoming (13376)

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
TNF	therapeutic_target	gene	1.00
P62	regulates	gene	1.00
GENES	contributes_to	gene	1.00
ATG5	activates	gene	1.00
GENES	expressed_in	gene	1.00
JAK2	activates	gene	1.00
DNA	biomarker_for	gene	1.00
C-JUN	activates	gene	1.00
Cancer	associated_with	disease	1.00
MITOCHONDRIAL DNA	associated_with	gene	1.00
Fibrosis	associated_with	disease	1.00
TFEB	activates	gene	1.00
APOE	associated_with	gene	1.00
MYC	activates	gene	1.00
BDNF	associated_with	gene	1.00
TRKB	activates	gene	1.00
GENES	regulates	gene	1.00
Stroke	associated_with	disease	1.00
Aging	associated_with	disease	1.00
P38	activates	gene	1.00
PTEN	inhibits	gene	1.00
TNF	associated_with	gene	1.00
PI3K	inhibits	gene	1.00
AKT	inhibits	gene	1.00
SIRT1	activates	gene	1.00
P62	interacts_with	gene	1.00
BCL-2	therapeutic_target	gene	1.00
GENES	interacts_with	gene	1.00
OVERVIEW	therapeutic_target	gene	1.00
DNA	associated_with	gene	1.00
TNF	expressed_in	gene	1.00
SIRT3	activates	gene	1.00
TREM2	activates	gene	1.00
BAX	inhibits	gene	1.00
LC3	associated_with	gene	1.00
PTEN	therapeutic_target	gene	1.00
TLR4	therapeutic_target	gene	1.00
Obesity	associated_with	disease	1.00
OPTN	interacts_with	gene	1.00
MTOR	therapeutic_target	gene	1.00
ERK1	activates	gene	1.00

Targeting Hypotheses (23)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.824	neurodegeneration	What are the mechanisms by which gut mic
STING Antagonists as ALS Therapeutics: Drug Repurposing	0.740	neuroinflammation	How does chronic cGAS/STING activation d
Liquid-to-Solid Transition Pathology Reveals Granule Weak Po	0.710	neurodegeneration	What determines the specificity of RNA-p
Conformational-Selective Blocking of Tau Uptake Reveals Ther	0.710	neurodegeneration	What is the therapeutic window between t
Hippocampal-Cortical Transcriptomic Divergence Reveals Accel	0.680	Alzheimer disease	Allen Mouse Brain Aging Atlas: cross-age

Stathmin-2 Splice Switching to Prevent Axonal Degeneration A	0.664	neurodegeneration	RNA binding protein dysregulation across
ALS-Linked OPTN/TBK1 Mutations Impair Phosphorylation Cascad	0.648	neurodegeneration	How do pathological stress granules in n
CDK5 Inhibition at Presynaptic Terminals Prevents Activity-D	0.640	neurodegeneration	Investigate prion-like spreading of tau
SYNJ1 Aggregation and Solubility Loss Impairs PI(4,5)P2 Cycl	0.621	neurodegeneration	What are the specific PTM changes in syn
Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulat	0.620	neurodegeneration	Gap 006 analysis (archived stub)
APOE4 preferentially signals through LRP1 over LDLR, alterin	0.610	neuroscience	APOE4-driven lipid metabolism dysregulat
ALS-Associated G3BP1 Mutations Shift Phase Separation Equili	0.610	neurodegeneration	How do disease-associated mutations in G
Aβ42 oligomers drive TDP-43 phosphorylation at s409/410 thro	0.595	neurodegeneration	What mechanisms drive TDP-43 pathology s
G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG	0.590	neurodegeneration	How do disease-associated mutations in G
ALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding Inte	0.585	neurodegeneration	How do pathological stress granules in n
PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5	0.584	neurodegeneration	How does PIKFYVE inhibition activate unc
C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by	0.562	neurodegeneration	How does PIKFYVE inhibition activate unc
H63D HFE Genotype-Guided Iron Chelation Therapy for Subset-S	0.550	-	Ferroptosis in ALS and motor neuron dise
N-acetylation Deficiency as Novel Metabolic Vulnerabilities	0.540	neurodegeneration	Gap 006 analysis (archived stub)
FUS-ALS-Specific Ferroptosis Vulnerability Through NCOA4-Med	0.480	-	Ferroptosis in ALS and motor neuron dise
Age-dependent downregulation of KPNA2 creates limbic neuron-	0.452	neurodegeneration	What mechanisms drive TDP-43 pathology s
Amyloid first impairs cholinergic terminals through alpha7 n	0.450	neurodegeneration	What determines the temporal sequence of
Human Serum Albumin-Mediated Displacement Creates False-Posi	0.136	molecular biology	Does Alectinib truly bind C1q directly w

Mentioning Analyses (30)

Scientific analyses that reference this entity

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (7)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
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
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
Opportunities and challenges of targeting cGAS-STING in cancer. [PMID:41486397]	Lu C, Wang W, Fu YX	Nat Rev Cancer	2026
cGAS-STING activation in Parkinson's Disease: From mechanisms to Disease-Modifyi [PMID:41500413]	Solomon J, Mandal S, Aran KR	Gene	2026
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
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
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

Debates (20)

Multi-agent debates referencing this entity

ALS

Understanding Entity Pages

Summary

Wiki Pages (21)

Betz Cells in Amyotrophic Lateral Sclerosis

ALS Failed Approaches Analysis

Rapamycin ALS Trial - mTOR Inhibition for Amyotrophic Lateral Sclerosis

Epigenetic Dysregulation Comparison -- AD/PD/ALS/FTD/HD

Pre-symptomatic Conversion Windows in ALS Genetic Risk Carriers

Lipid Metabolism Dysfunction Comparison — AD/PD/ALS/FTD/HD

Autophagy-Lysosomal Impairment Comparison — AD/PD/ALS/FTD/HD

Neuroinflammation Across AD, PD, ALS, FTD, and HD

ALS-FTD Spectrum

Amyotrophic Lateral Sclerosis (ALS)

Autophagy Failure Comparison -- AD/PD/ALS/FTD/HD

ALS Pipeline

Ion Channel Dysfunction in ALS

ALS Combination Therapy Matrix

ALS Biomarker-to-Mechanism Mapping

ALS RNA Metabolism and Proteostasis Failure

ALS Regional Onset and Spread: Network-Level Staging Model

FTD-ALS Spectrum

C9orf72→RNA/Dipeptide Repeat Pathology→ALS/FTD — Causal Chain

SOD1 Superoxide Dismutase 1 ALS Causal Chain

High-Dose Vitamins ALS Trial

Pathway Diagram

Outgoing (5367)

Incoming (13376)

Targeting Hypotheses (23)

Mentioning Analyses (30)

Which specific factors in conditioned medium from healthy astrocytes rescue moto

Comparative epigenetic signatures: DNA methylation age acceleration and histone

Comparative epigenetic signatures: DNA methylation age acceleration and histone

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

Microglial subtypes in neurodegeneration — friend vs foe

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

test debate

How does FUS loss-of-function in TAZ regulation contribute to ALS/FTD pathogenes

How do ALS-associated OPTN mutations mechanistically disrupt Rab8a binding and c

What molecular mechanisms enable functional recovery and muscle re-innervation a

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

RNA binding protein dysregulation across ALS FTD AD

How do non-cell autonomous effects of autophagy dysfunction contribute to ALS pa

What are the neuron-specific effects of ALS-causing mutations on autophagy machi

What upstream mechanisms cause TDP-43 to trigger mPTP opening and can this be th

What mechanisms underlie neuronal resistance to autophagy induction compared to

What mechanisms drive TDP-43 pathology specifically in Alzheimer's disease versu

How does chronic cGAS/STING activation downstream of TDP-43 contribute to progre

What determines the specificity of TDP-43-induced mitochondrial DNA release for

How do pathological stress granules in neurodegeneration escape TRIM21/autophagy

How do disease-associated mutations in G3BP1 or its binding partners alter stres

CRISPR-based therapeutic approaches for neurodegenerative diseases

Gap 006 analysis (archived stub)

CRISPR-based therapeutic approaches for neurodegenerative diseases

Microglial subtypes in neurodegeneration — friend vs foe

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 phase separation therapeutics for ALS-FTD

Experiments (0)

Related Papers (7)

Debates (20)

Which specific factors in conditioned medium from healthy astrocytes rescue moto

Analysis for knowledge gap 006 in the neurodegeneration domain.

The study establishes G3BP1's role as a tunable switch for stress granule assemb

The study shows TRIM21 and autophagy receptors can eliminate both physiological

While the study establishes TDP-43 triggers mtDNA release via mPTP to activate c

The study identifies cGAS/STING activation as a consequence of TDP-43-mediated m

TDP-43 inclusions occur in AD, ALS, and FTLD but the pathogenic mechanisms leadi

The abstract identifies that neurons show resistance to autophagy induction, but

While the study demonstrates TDP-43 triggers mPTP-mediated mtDNA release, the mo

While ALS-causing mutations impair autophagy factors, the neuron-specific effect