gene

AUTOPHAGY

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AUTOPHAGY: 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.

14804Connections

30Hypotheses

4Analyses

50Outgoing

50Incoming

20Experiments

4Debates

Summary

Autophagy is an evolutionarily conserved cellular degradation pathway that removes damaged organelles and misfolded proteins through lysosomal degradation. In neurodegeneration, autophagy dysfunction contributes to accumulation of toxic protein aggregates including amyloid-beta, tau, alpha-synuclein, and TDP-43. Key regulators include mTOR, AMPK, Beclin-1, and TFEB. Enhancing autophagy is a major therapeutic strategy for neurodegenerative diseases.

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🧬 Gene Info

Gene Symbol	AUTOPHAGY
Aliases	Autophagy-lysosomal pathway, Cellular self-eating
Function	Protein degradation; Organelle turnover; Quality control
Pathways	mTOR pathway, AMPK signaling, Beclin-1 complex
Associated Diseases	Aging, Als, Alzheimer, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	3-Methyladenine, BEVACIZUMAB, BPA, COENZYME Q10, CURCUMIN, Cyclocreatine
Interactions	6-OHDA, ABCA1, ABCD3, ABCG1, ABCG2, ACC
KG Connections	8162 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

Autophagy Types in Neurodegeneration

mechanism · 2684 words

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AUTOPHAGY

pathway · 554 words

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Pathway Diagram

graph TD
    subgraph Pathology["Pathology"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| CANCER["CANCER"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| AGING["AGING"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| NEURON["NEURON"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| MICROGLIA["MICROGLIA"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| LYSOSOME["LYSOSOME"]
        AUTOPHAGY["AUTOPHAGY"] -->|"associated with"| MITOCHONDRIA["MITOCHONDRIA"]
    end
    subgraph Signaling["Signaling"]
        AUTOPHAGY["AUTOPHAGY"] -->|"regulates"| AGING_1["AGING"]
        AUTOPHAGY["AUTOPHAGY"] -.->|"inhibits"| P62["P62"]
        AUTOPHAGY["AUTOPHAGY"] -->|"regulates"| CANCER_2["CANCER"]
        MTORC1["MTORC1"] -.->|"inhibits"| AUTOPHAGY["AUTOPHAGY"]
        ULK1["ULK1"] -->|"regulates"| AUTOPHAGY["AUTOPHAGY"]
        AMPK["AMPK"] -->|"activates"| AUTOPHAGY["AUTOPHAGY"]
        SIRT1["SIRT1"] -->|"activates"| AUTOPHAGY["AUTOPHAGY"]
        ROS["ROS"] -->|"activates"| AUTOPHAGY["AUTOPHAGY"]
        P62_3["P62"] -->|"regulates"| AUTOPHAGY["AUTOPHAGY"]
    end
    style AUTOPHAGY fill:#4a1a6b,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
    style CANCER fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AGING fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AGING_1 fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style P62 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style CANCER_2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style NEURON fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MICROGLIA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style LYSOSOME fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MITOCHONDRIA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MTORC1 fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ULK1 fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AMPK fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style SIRT1 fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ROS fill:#5d4400,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style P62_3 fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0

Outgoing (6698)

Target	Relation	Type	Str
Tumor	inhibits	disease	1.00
Apoptosis	inhibits	pathway	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
Autophagy	contributes_to	pathway	1.00
Cancer	inhibits	disease	1.00
Autophagy	inhibits	pathway	1.00
MITOCHONDRIA	associated_with	gene	1.00
Inflammation	regulates	disease	1.00
Epigenetic	activates	pathway	1.00
INFLAMMATION	regulates	gene	1.00
Neuroinflammation	activates	disease	1.00
Als	inhibits	disease	1.00
Diabetes	therapeutic_target	disease	1.00
Inflammation	activates	disease	1.00
CANCER	regulates	gene	1.00
LYSOSOME	associated_with	gene	1.00
Autophagy	activates	pathway	1.00
Autophagy	associated_with	pathway	1.00
Mtor	regulates	pathway	1.00
Als	therapeutic_target	disease	1.00
AMPK	activates	gene	1.00
Immune Response	regulates	pathway	1.00
Mtor	therapeutic_target	pathway	1.00
Autophagy	therapeutic_target	pathway	1.00
AGING	associated_with	phenotype	1.00
Lipid Metabolism	regulates	pathway	1.00
Cancer	activates	disease	1.00
MTORC1	activates	gene	1.00
Apoptosis	activates	pathway	1.00
Cardiovascular	activates	disease	1.00
ferroptosis	regulates	phenotype	1.00
P62	inhibits	gene	1.00
NEURON	associated_with	gene	1.00
MICROGLIA	associated_with	gene	1.00
OXIDATIVE STRESS	associated_with	gene	1.00
neuroinflammation	associated_with	process	1.00
TAU	associated_with	gene	1.00
Epigenetic	regulates	pathway	1.00
AGING	regulates	phenotype	1.00
Mtor	inhibits	pathway	1.00
Als	activates	disease	1.00
LC3	associated_with	gene	1.00
cancer	associated_with	disease	1.00
neurodegeneration	associated_with	disease	1.00
Mtor	activates	pathway	1.00
Innate Immunity	regulates	pathway	1.00
Carcinoma	therapeutic_target	disease	1.00
Oxidative Stress	regulates	pathway	1.00
Autophagy	regulates	pathway	1.00
Parkinson	associated_with	disease	1.00

Incoming (8106)

Source	Relation	Type	Str
GFP	associated_with	gene	1.00
ROS	regulates	gene	1.00
TNF-Α	inhibits	gene	1.00
MITOCHONDRIA	interacts_with	gene	1.00
BCL-2	activates	gene	1.00
AMYLOID	activates	gene	1.00
NEURODEGENERATIVE DISORDERS	associated_with	gene	1.00
ALS	associated_with	gene	1.00
PARKINSON'S DISEASE	regulates	gene	1.00
OXIDATIVE STRESS	inhibits	gene	1.00
LC3	associated_with	gene	1.00
GFP	associated_with	gene	1.00
AKT	associated_with	gene	1.00
CYTOKINES	inhibits	gene	1.00
ATG9A	associated_with	gene	1.00
LC3	activates	gene	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
NEUROTOXICITY	activates	gene	1.00
Parkinson	therapeutic_target	disease	1.00
ATG	activates	gene	1.00
Neurodegeneration	regulates	disease	1.00
Aging	activates	disease	1.00
P62	associated_with	gene	1.00
IL-6	inhibits	gene	1.00
Neurodegeneration	therapeutic_target	disease	1.00
P62	associated_with	gene	1.00
Alzheimer	associated_with	disease	1.00
Inflammation	therapeutic_target	disease	1.00
P62	regulates	gene	1.00
MTOR	associated_with	gene	1.00
ULK1	activates	protein	1.00
Tumor	regulates	disease	1.00
DNA	activates	gene	1.00
Ischemia	activates	disease	1.00
Aging	therapeutic_target	disease	1.00
GENES	contributes_to	gene	1.00
GENES	expressed_in	gene	1.00
MITOPHAGY	associated_with	gene	1.00
Als	therapeutic_target	disease	1.00
AMPK	regulates	gene	1.00
Cancer	therapeutic_target	disease	1.00
Cancer	regulates	disease	1.00
Tumor	therapeutic_target	disease	1.00
GENES	associated_with	gene	1.00
LC3B	activates	gene	1.00
Aging	inhibits	disease	1.00
Als	associated_with	disease	1.00
ATG5	inhibits	gene	1.00
CGAS	activates	gene	1.00
ROS	regulates	gene	1.00

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Autophagy-Senescence Axis Therapeutic Window	0.921	-	Senescent cell clearance as neurodegener
Transcriptional Autophagy-Lysosome Coupling	0.882	neurodegeneration	Autophagy-lysosome pathway convergence a
APOE-Dependent Autophagy Restoration	0.850	neurodegeneration	Mechanistic role of APOE in neurodegener
Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated	0.843	molecular neurobiology	View
VCP-Mediated Autophagy Enhancement	0.787	neurodegeneration	Tau propagation mechanisms and therapeut

Closed-loop tACS targeting entorhinal cortex layer II SST in	0.784	Alzheimer's disease	Circuit-level neural dynamics in neurode
TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle	0.772	neurodegeneration	How do different organelle-specific auto
Circadian Clock-Autophagy Synchronization	0.763	neurodegeneration	Sleep disruption as cause and consequenc
H2: Impaired Autophagy Receptor Recruitment Traps G3BP1 Gran	0.737	neurodegeneration	How do pathological stress granules tran
VCP/p97 ATPase mutations impair extraction of ubiquitinated	0.720	neurodegeneration	What are the neuron-specific effects of
C9orf72 DPRs Impair Autophagy Receptor Docking on Stress Gra	0.717	neurodegeneration	How do pathological stress granules in n
p21^Cip1 Phospho-State as Autophagy Responsiveness Predictor	0.710	molecular biology	What is the optimal therapeutic window t
Autophagy-Lysosomal Degradation of IBA1 in Stressed Microgli	0.706	neuroinflammation	What causes IBA1 low/negative microglia
TFEB-Independent Autophagy Bypass	0.697	neurodegeneration	Does TFEB dysfunction cause neurodegener
mTORC1 Reactivation as Autophagy-Senescence Divergence Point	0.685	molecular biology	What is the optimal therapeutic window t
GDF15-GFRAL Axis as Systemic Autophagy-Senescence Integrator	0.653	molecular biology	What is the optimal therapeutic window t
Radiation drives pericyte senescence through lysosome acidif	0.652	neurodegeneration	What specific autophagy pathways are def
p62 Liquid-Liquid Phase Separation Nucleates Cross-Organelle	0.649	neurodegeneration	How do different organelle-specific auto
H7: mTOR Hyperactivity Blocks Autophagy, Permitting Tau Seed	0.640	neurodegeneration	Entorhinal cortex layer II vulnerability
G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclu	0.633	neurodegeneration	What determines the spatial organization
Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic	0.614	molecular biology	What is the optimal therapeutic window t
Mitophagy collapse via PINK1-PRKN is the primary autophagy l	0.614	neurodegeneration	What specific autophagy pathways are def
FUS Mutations Alter Stress Granule Material Properties to Co	0.613	neurodegeneration	How do pathological stress granules in n
P2RY12-mediated autophagy inhibition in cerebral VSMCs impai	0.605	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
Autophagy Activation ULK1/VPS34 (H3): Lipid Routing to Lysos	0.600	neurodegeneration	Does restoring neuronal AMPK activity re
P2RY12-driven autophagy impairment in cerebral VSMCs mediate	0.585	neurodegeneration	How does P2RY12-mediated VSMC dysfunctio
Chronic mTORC1-ULK1 signaling blocks autophagy initiation in	0.578	neurodegeneration	What specific autophagy pathways are def
Sequential TRPML1 Activation Following Autophagy Priming	0.575	neurodegeneration	Does TRPML1 enhancement cause therapeuti
VPS34 Complex I Subunit Heterogeneity Dictates Organelle-Spe	0.571	neurodegeneration	How do different organelle-specific auto
VCP-Mediated Autophagy Enhancement	0.571	Alzheimer's Disease	Tau propagation mechanisms and therapeut

Mentioning Analyses (4)

Scientific analyses that reference this entity

Experiments (20)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Circadian gene expression effects of SD vs ketamine	exploratory	depression	0.950	0.00	C57BL/6J mice	proposed	N/A
iPSC-NPC effects on astrocytes in vitro ICH model	exploratory	intracerebral hemorrhage	0.900	0.00	in vitro ICH cell culture mode	proposed	N/A
CLOCK/BMAL1 regulation of ICC autophagy in GERD model	exploratory	gastroesophageal reflux diseas	0.900	0.00	primary esophageal interstitia	proposed	N/A
AMPK knockdown validation experiment	exploratory	intracerebral hemorrhage	0.880	0.00	astrocyte cell culture	proposed	N/A
P2RY12-MTOR pathway interaction in VSMCs	exploratory	atherosclerosis	0.850	0.00	cultured VSMCs	proposed	N/A
iPSC-NPC transplantation in ICH animal model	validation	intracerebral hemorrhage	0.850	0.00	animal ICH model	proposed	N/A
Autophagy Enhancement Drug Screening for Neurodegeneration	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
Chaperone-Mediated Autophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Macroautophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Validate Mitochondria-Lysosome Contact Site Dysfunction in PD	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Mutant Huntingtin (mHTT) Clearance Mechanisms — Therapeutic Target Val	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
MLCS Quantification in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Presymptomatic GRN Carrier Intervention Timing — Biomarker-Guided Ther	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeu	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,730,000
Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) an	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Proposed experiment from debate on Epigenetic clocks and biological ag	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Circadian-Vascular-Metabolic Syndrome (CVMS) Intervention Trial	clinical	Neurodegeneration	0.400	0.50	human	proposed	$3,900,000
Experiment Index	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,280,000
N-of-1 Clinical Trial Design for CBS/PSP	clinical	ALS	0.400	0.50	human	proposed	$5,460,000
Normal Aging to Alzheimer's Disease Transition Trigger — Identifying t	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,280,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Hepatocyte FoxO1 Deficiency Protects From Liver Fibrosis via Reducing Inflammati [PMID:37678798]	Pan Q, Gao M, Kim D, Ai W, Yang W, Jiang	Cell Mol Gastroenterol Hepatol	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and inv [PMID:35176466]	Zhang L, Liang B, Xu H, Gong Y, Hu W, Ji	J Ethnopharmacol	2022	1
Improved T-cell Receptor Diversity Estimates Associate with Survival and Respons [PMID:33177107]	Bortone DS, Woodcock MG, Parker JS, Vinc	Cancer Immunol Res	2021	1
Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK [PMID:31693892]	Wang Y, An H, Liu T, Qin C, Sesaki H, Gu	Cell Rep	2019	1
AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking Sy [PMID:30057310]	Song X, Zhu S, Chen P, Hou W, Wen Q, Liu	Curr Biol	2018	1
Obestatin controls the ubiquitin-proteasome and autophagy-lysosome systems in gl [PMID:28675664]	Cid-Díaz T, Santos-Zas I, González-Sánch	J Cachexia Sarcopenia Muscle	2017	1
Spatiotemporal profile of postsynaptic interactomes integrates components of com [PMID:28671696]	Li J, Zhang W, Yang H, Howrigan DP, Wilk	Nat Neurosci	2017	1
Core Concept: The Internet of Things and the explosion of interconnectivity. [PMID:27702874]	Ornes S	Proc Natl Acad Sci U S A	2016	1
Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and T [PMID:41833042]	["Lyu G", "Li D"]	CNS & neurological disorders d	2026	0
PTEN loss drives B7H3 upregulation via the mTORC2/FOXO/c-Myc axis to promote tum [PMID:41920736]	Wang Z, Jin N, Li X, Ma X, Feng Y, Yin K	Cell reports	2026	0
Epigenetics and the gut-brain axis: Insights into DNA methylation, aging, and Al [PMID:41886887]	Kumar V, Shukla R, Gangani S, Joseph R,	The Journal of pharmacology an	2026	0
Replating Induces mTOR-Dependent Rescue of Protein Synthesis in Charcot-Marie-To [PMID:41876253]	Koenig J, McGuire A, Homedan Y, Alberhas	eNeuro	2026	0
Effects of circadian rhythms on antimicrobial peptide concentrations in lactatin [PMID:41923233]	Liang ZL, Nii T, Sugino T, Isobe N	BMC veterinary research	2026	0
Circadian synchronization between diet and gut microbiota in modulating host's h [PMID:41914045]	["Ma J", "Zhen Y", "Weng Y", "Lin J", "Z	Gut microbes	2026	0
S-equol promotes ferroptosis in triple negative breast cancer by coordinating NC [PMID:41925800]	Ni F, Huang Z, Cui Y, Huang P, Xue Z, Hu	Molecular and cellular biochem	2026	0
Randomized controlled trial of resistance exercise and brain aging clocks. [PMID:41665740]	["Gonzalez-Gomez R", "Demnitz N", "Coron	GeroScience	2026	0
Mammalian lipophagy: process and function. [PMID:41681129]	Zhao R, Dai E, Kang R, Liu J, Klionsky D	Autophagy	2026	0
TAZ alleviates ischemic stroke injury by activating Foxo1: Usp1-mediated deubiqu [PMID:41921828]	["Xin Y", "Sun Y", "Pan E", "Li M", "Che	Free radical biology & medicin	2026	0
Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clin [PMID:41396614]	Brown CA, Mundada NS, Cousins KAQ, Sadeg	JAMA neurology	2026	0

Debates (4)

Multi-agent debates referencing this entity

AUTOPHAGY

Understanding Entity Pages

Summary

Wiki Pages (2)

Autophagy Types in Neurodegeneration

AUTOPHAGY

Pathway Diagram

Outgoing (6698)

Incoming (8106)

Targeting Hypotheses (30)

Mentioning Analyses (4)

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

Do tau-containing vesicles exhibit unique surface glycosylation patterns that di

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

Does TFEB dysfunction cause neurodegeneration or represent a compensatory respon

Experiments (20)

Related Papers (20)

Debates (4)

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

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

Do tau-containing vesicles exhibit unique surface glycosylation patterns that di

The debate highlighted TFEB's role in mitochondrial-lysosomal coupling but could