phenotype

ROS

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about ROS: 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.

4245Connections

30Hypotheses

8Analyses

50Outgoing

50Incoming

0Experiments

9Debates

Summary

ROS is a phenotype associated with neurodegeneration research. Key relationships include: activates, interacts with, regulates. Associated with AD, ALI, ALS. Connected to 1918 entities in the SciDEX knowledge graph.

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Wiki Pages (9)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    subgraph Signaling["Signaling"]
        ROS["ROS"] -->|"activates"| NRF2["NRF2"]
        ROS["ROS"] -->|"activates"| AUTOPHAGY["AUTOPHAGY"]
        ROS["ROS"] -->|"activates"| FERROPTOSIS_1["FERROPTOSIS"]
        ROS["ROS"] -->|"regulates"| PI3K["PI3K"]
        ROS["ROS"] -->|"activates"| ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
        ROS["ROS"] -->|"regulates"| GENES["GENES"]
        ROS["ROS"] -->|"activates"| ALZHEIMER["ALZHEIMER"]
        SLC7A11["SLC7A11"] -.->|"inhibits"| ROS["ROS"]
        AUTOPHAGY_2["AUTOPHAGY"] -->|"activates"| ROS["ROS"]
        OXIDATIVE_STRESS["OXIDATIVE STRESS"] -->|"activates"| ROS["ROS"]
        MITOPHAGY["MITOPHAGY"] -->|"activates"| ROS["ROS"]
        SLC7A11_3["SLC7A11"] -->|"activates"| ROS["ROS"]
        BAX["BAX"] -->|"activates"| ROS["ROS"]
    end
    subgraph Pathology["Pathology"]
        ROS["ROS"] -->|"causes"| DNA["DNA"]
        ROS["ROS"] -->|"causes"| FERROPTOSIS["FERROPTOSIS"]
    end
    style ROS fill:#5d4400,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
    style NRF2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AUTOPHAGY fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style DNA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style FERROPTOSIS fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style FERROPTOSIS_1 fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style PI3K fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER_S_DISEASE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style GENES fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style SLC7A11 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AUTOPHAGY_2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style OXIDATIVE_STRESS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MITOPHAGY fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style SLC7A11_3 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style BAX fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0

Outgoing (2540)

Target	Relation	Type	Str
TNF-Α	inhibits	gene	1.00
Tumor	inhibits	disease	1.00
INFLAMMATION	inhibits	gene	1.00
Ferroptosis	inhibits	pathway	1.00
Oxidative Stress	associated_with	pathway	1.00
NEUROINFLAMMATION	activates	gene	1.00
DNA	therapeutic_target	gene	1.00
FERROPTOSIS	inhibits	gene	1.00
Als	inhibits	disease	1.00
CYTOKINES	activates	gene	1.00
MITOCHONDRIAL DYSFUNCTION	activates	gene	1.00
Aging	associated_with	disease	1.00
NEUROTOXICITY	activates	gene	1.00
GENES	activates	gene	1.00
Als	activates	disease	1.00
IL-6	activates	gene	1.00
Mitophagy	activates	pathway	1.00
Autophagy	associated_with	pathway	1.00
Inflammation	causes	disease	1.00
Mtor	activates	pathway	1.00
Inflammation	activates	disease	1.00
Differentiation	activates	pathway	1.00
Invasion	activates	pathway	1.00
MTDNA	activates	gene	1.00
LC3	activates	gene	1.00
Type 2 Diabetes	activates	disease	1.00
Cancer	causes	disease	1.00
CANCER	inhibits	gene	1.00
CANCER	causes	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
GENES	regulates	gene	1.00
ALZHEIMER	activates	gene	1.00
MITOCHONDRIA	regulates	gene	1.00
DNA	activates	gene	1.00
AUTOPHAGY	activates	pathway	1.00
Ferroptosis	activates	pathway	1.00
Alzheimer	activates	disease	1.00
Neuroinflammation	activates	disease	1.00
NRF2	activates	gene	1.00
Cancer	inhibits	disease	1.00
INFLAMMATION	activates	gene	1.00
Ischemia	activates	disease	1.00
DNA	causes	gene	1.00
Inflammation	inhibits	disease	1.00
Autophagy	regulates	pathway	1.00
APOPTOSIS	regulates	gene	1.00
Cancer	associated_with	disease	1.00
Oxidative Phosphorylation	activates	pathway	1.00
DNA	regulates	gene	1.00
Oxidative Stress	causes	pathway	1.00

Incoming (1705)

Source	Relation	Type	Str
OXIDATIVE STRESS	activates	gene	1.00
GPX4	activates	gene	1.00
GPX4	inhibits	gene	1.00
AUTOPHAGY	activates	gene	1.00
PINK1	activates	gene	1.00
BAX	activates	gene	1.00
MITOPHAGY	activates	gene	1.00
SLC7A11	inhibits	gene	1.00
SLC7A11	activates	gene	1.00
mechanisms-metal-ion-toxicity	describes	wiki	1.00
NRF2	activates	gene	1.00
ATG	associated_with	gene	1.00
MITOCHONDRIAL DYSFUNCTION	activates	gene	1.00
APOPTOSIS	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
KRAS	activates	gene	0.95
Rotenone	upregulates	drug	0.95
Quercetin	modulates	compound	0.95
ENDOTHELIAL CELLS	activates	cell_type	0.95
Rotenone	upregulates	compound	0.95
Manganese	activates	compound	0.95
celastrol	promotes	compound	0.95
Nac	inhibits	compound	0.90
SOD	downregulates	enzyme	0.90
Autophagy	downregulates	process	0.90
NADPH	activates	gene	0.90
DNA	disrupts	gene	0.90
ETC subunits	causes	protein_complex	0.90
NAC	inhibits	drug	0.90
PGC1Α	regulates	entity	0.90
FDX1	inhibits	gene	0.90
mitochondrial_dysfunction	associated_with	phenotype	0.90
SLC7A11	downregulates	gene	0.90
OXIDATIVE STRESS	therapeutic_target	gene	0.90
GPX4	associated_with	gene	0.90
PI3K	activates	gene	0.90
AUTOPHAGY	associated_with	gene	0.90
TNF-Α	activates	gene	0.90
116B	associated_with	compound	0.88
AKT	modulates	protein	0.85
HSPA5	inhibits	entity	0.85
Ulva Sp.	inhibits	drug	0.85
Reductive Stress Response	regulates	pathway	0.85
ROS	encodes	gene	0.85
AUTOPHAGY	inhibits	pathway	0.84
MITOPHAGY	regulates	pathway	0.84
MITOPHAGY	inhibits	pathway	0.84
JNK	regulates	gene	0.80
NRF2	regulates	entity	0.80
ERN1	activates	gene	0.80

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegener	0.892	neurodegeneration	Gene expression changes in aging mouse b
TDP-43 RNA-proteostasis failure across ALS, FTD, and AD/LATE	0.828	multi	Cross-disease neurodegeneration mechanis
Gamma entrainment repairs cross-regional phase-amplitude cou	0.826	alzheimers	Gamma entrainment therapy to restore hip
SNCA conformer propagation across PD, DLB, and MSA	0.820	multi	Cross-disease neurodegeneration mechanis
C9ORF72 autophagy-lysosome collapse across ALS and FTD	0.816	multi	Cross-disease neurodegeneration mechanis

MAPT tau seeding and release across AD, FTD, and PD-spectrum	0.812	multi	Cross-disease neurodegeneration mechanis
TREM2-APOE microglial state switching across AD, ALS, and PD	0.804	multi	Cross-disease neurodegeneration mechanis
NLRP3 inflammasome amplification across AD and PD proteinopa	0.800	multi	Cross-disease neurodegeneration mechanis
PINK1/Parkin mitophagy failure across PD, AD, and ALS	0.796	multi	Cross-disease neurodegeneration mechanis
Stress-granule RNA-binding protein phase transition across A	0.780	multi	Cross-disease neurodegeneration mechanis
TBK1-OPTN-p62 selective autophagy failure across ALS, FTD, a	0.776	multi	Cross-disease neurodegeneration mechanis
Alpha-gamma cross-frequency coupling enhancement to restore	0.775	alzheimers	Circuit-level neural dynamics in neurode
TREM2 Crosstalk and Synergistic Activation of Phagocytic Tra	0.761	neuroinflammation	What molecular mechanisms mediate SPP1-i
TDP-43 Proteinopathy as a Cross-Disease Pathological Substra	0.760	neurodegeneration	Cross-disease neurodegeneration mechanis
GRN/progranulin lysosomal insufficiency across FTD, ALS-spec	0.756	multi	Cross-disease neurodegeneration mechanis
TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming	0.748	neurodegeneration	Gene expression changes in aging mouse b
APOE Isoform Expression Across Glial Subtypes	0.743	alzheimers	SEA-AD Gene Expression Profiling — Allen
NRF2 failure lowers antioxidant reserve and permits recurren	0.740	neurodegeneration	What mechanisms drive the self-amplifyin
VPS35 retromer activation prevents endosomal tau templating	0.740	neurodegeneration	Which tau propagation mechanism predomin
TREM2 Agonism to Restore Microglial Phagocytosis Across Both	0.735	neurodegeneration	Why have anti-Aβ clinical trials failed
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegen	0.716	neurodegeneration	TREM2 in Alzheimer's Disease: Mechanisms
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence	0.713	neurodegeneration	Gene expression changes in aging mouse b
NRF2 Activation Provides Neuroprotection Across ALS, AD, and	0.710	neurodegeneration	Test Preregistration Analysis
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegene	0.708	neurodegeneration	Gene expression changes in aging mouse b
Mitochondrial-Nuclear Epigenetic Cross-Talk Restoration	0.701	neurodegeneration	Epigenetic reprogramming in aging neuron
Cross-Seeding Prevention Strategy	0.689	neurodegeneration	RNA binding protein dysregulation across
Microglial NOX2 establishes an inflammatory ROS propagation	0.680	neurodegeneration	What mechanisms drive the self-amplifyin
Soluble LRP1 (sLRP1) Ectodomain Shedding as a Blood-Based In	0.680	-	What blood-brain barrier permeability ch
OPC exhaustion and failed remyelination in progressive multi	0.670	neurodegeneration	Test
LDLR-Mediated Neurosteroid Precursor Delivery Strategy	0.000	neuropharmacology	What is the actual quantitative contribu

Mentioning Analyses (8)

Scientific analyses that reference this entity

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

neurodegeneration | 2026-04-27 | 0 hypotheses

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.387

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.720

Proteomics Differential Expression in AD CSF and Brain Tissue

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.865

How does PSEN2 mechanistically regulate α-synuclein expression and pathology in

neurodegeneration | 2026-04-13 | 0 hypotheses

Experiments (0)

Experimental studies targeting or related to this entity

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

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Mic [PMID:28930663]	Krasemann S, Madore C, Cialic R, Baufeld	Immunity	2017	1
Isoginkgetin antagonizes ALS pathologies in its animal and patient iPSC models v [PMID:41094045]	Li A, Huang S, Cao SQ, Lin J, Zhao L, Yu	EMBO molecular medicine	2025	0
Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Park [PMID:36262883]	Unknown	Frontiers in aging neuroscienc	2023	0
TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP- [PMID:34916658]	Xie M, Liu YU, Zhao S, Zhang L, Bosco DB	Nature neuroscience	2022	0
PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. [PMID:33168089]	Quinn PMJ, Moreira PI, Ambrósio AF, Alve	Acta neuropathologica communic	2020	0
Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive defi [PMID:30742114]	Unknown	Nature neuroscience	2019	0
NLRP3 inflammasome activation drives tau pathology. [PMID:31748742]	["Ising C", "Venegas C", "Zhang S", "Sch	Nature	2019	0
Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodeg [PMID:30381407]	Gordon R, Albornoz EA, Christie DC, Lang	Science translational medicine	2018	0
LRRK2 Promotes Tau Accumulation, Aggregation and Release. [PMID:26014385]	Unknown	Molecular neurobiology	2017	0
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Prom [PMID:28817800]	["Mackenzie Ian R", "Nicholson Alexandra	Neuron	2017	0
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. [PMID:25611507]	["Pickrell Alicia M", "Youle Richard J"]	Neuron	2015	0
Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem prote [PMID:23455423]	Unknown	Nature	2013	0
TREM2 variants in Alzheimer's disease. [PMID:23150934]	Rita Guerreiro, Aleksandra Wojtas, Jose	The New England journal of med	2013	0
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS [PMID:23254930]	Heneka MT, Kummer MP, Stutz A, Delekate	Nature	2013	0
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS [PMID:23254930]	["Heneka Michael T", "Kummer Markus P",	Nature	2013	0
A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-lin [PMID:21944779]	Unknown	Neuron	2011	0
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chro [PMID:21944778]	["DeJesus-Hernandez Mariely", "Mackenzie	Neuron	2011	0
Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and A [PMID:18322368]	Unknown	Neuro-degenerative diseases	2008	0
TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. [PMID:17469117]	Unknown	Annals of neurology	2007	0
Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic latera [PMID:17023659]	Unknown	Science (New York, N.Y.)	2006	0

Debates (9)

Multi-agent debates referencing this entity

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

closed · Rounds: 6 · Score: 0.62 · 2026-04-27

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

completed · Rounds: 5 · Score: 0.50 · 2026-04-25

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

closed · Rounds: 4 · Score: 0.68 · 2026-04-25

The study shows P2RY12 regulates VSMC foam cell formation but doesn't explain wh

closed · Rounds: 4 · Score: 0.66 · 2026-04-21

While the study demonstrates both NF-κB pathway activation and increased C1qa ex

closed · Rounds: 4 · Score: 0.74 · 2026-04-21

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Which proteins are differentially expressed in AD CSF and brain tissue, and do t

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

Is a 12-protein CSF panel superior to existing plasma p-tau217 for clinical AD p

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

The study shows PSEN2 is essential in cortical and dopaminergic neurons and regu

closed · Rounds: 4 · Score: 0.68 · 2026-04-16

Related Research

Hypotheses and analyses mentioning ROS in their description or question text

ROS

Understanding Entity Pages

Summary

Wiki Pages (9)

Mitochondrial Dysfunction Hub

FNP-223 PROSPER Trial - Phase 2 in Progressive Supranuclear Palsy

Reactive Oxygen Species (ROS) Pathway

FNP-223 PROSPER Trial - Phase 2 in Progressive Supranuclear Palsy

PROSAP1 - Proline-Rich Synaptic-Associated Protein 1 (SHANK2)

PROS1 — Protein S (Vitamin K-Dependent Protein S)

Religious Orders Study and Memory and Aging Project (ROS/MAP)

Reactive Oxygen Species (ROS)

Reactive Oxygen Species (ROS)

Pathway Diagram

Outgoing (2540)

Incoming (1705)

Targeting Hypotheses (30)

Mentioning Analyses (8)

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

Proteomics Differential Expression in AD CSF and Brain Tissue

How does PSEN2 mechanistically regulate α-synuclein expression and pathology in

How does sevoflurane-induced NF-κB activation specifically trigger complement ca

What determines P2RY12 receptor expression/activity specifically in VSMCs during

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

Experiments (0)

Related Papers (20)

Debates (9)

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

The study shows P2RY12 regulates VSMC foam cell formation but doesn't explain wh

While the study demonstrates both NF-κB pathway activation and increased C1qa ex

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

Which proteins are differentially expressed in AD CSF and brain tissue, and do t

Is a 12-protein CSF panel superior to existing plasma p-tau217 for clinical AD p

The study shows PSEN2 is essential in cortical and dopaminergic neurons and regu

Related Research

MAPT tau seeding and release across AD, FTD, and PD-spectrum disease

TREM2-APOE microglial state switching across AD, ALS, and PD

NLRP3 inflammasome amplification across AD and PD proteinopathy

PINK1/Parkin mitophagy failure across PD, AD, and ALS

Stress-granule RNA-binding protein phase transition across ALS and FTD

TBK1-OPTN-p62 selective autophagy failure across ALS, FTD, and PD-like proteotox

Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical mem

TREM2 Crosstalk and Synergistic Activation of Phagocytic Transcriptome

TDP-43 Proteinopathy as a Cross-Disease Pathological Substrate

GRN/progranulin lysosomal insufficiency across FTD, ALS-spectrum stress, and AD

TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming

APOE Isoform Expression Across Glial Subtypes

NRF2 failure lowers antioxidant reserve and permits recurrent mitochondrial ROS

VPS35 retromer activation prevents endosomal tau templating across all brain reg

TREM2 Agonism to Restore Microglial Phagocytosis Across Both Pathologies