protein

TFEB

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TFEB: 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.

3008Connections

22Hypotheses

22Analyses

50Outgoing

50Incoming

8Experiments

20Debates

Summary

A protein referenced in 2 knowledge graph relationships. Key connections: promotes lysosomal_biogenesis (mechanism); semaglutide (drug) activates.

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🔬 Protein Info

Gene Symbol	TFEB
Aliases	Transcription Factor EB
Protein Type	Transcription Factor
Target Class	Protein
Function	TFEB is constitutively expressed in most cell types, with highest expression in tissues with high lysosomal activity including:
Mechanism of Action	Prioritized from 1 SciDEX hypotheses, including: The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction
Primary Expression	most cell types, with highest expression in tissues with high lysosomal activity including:
Druggability	Undruggable (0.23)
Molecular Weight	53 kDa
Pathways	mTOR
GeneCards	TFEB
Human Protein Atlas	TFEB
Metabolic decline in neurodegeneration	Brain glucose hypometabolism precedes clinical symptoms by decades; insulin resistance is a risk factor for AD and PD[@brain2023]
TFEB as master regulator	TFEB controls lysosome biogenesis, autophagy, and mitochondrial function—processes that decline with age and neurodegeneration[@tfeb2022]
Orthogonal mechanisms	GLP-1 agonists work via hormonal signaling (incretin effect); TFEB activators work via nuclear transcription[@tfeb2022a]
Associated Diseases	aging, Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	bortezomib, curcumin, CURCUMIN, digoxin, ELTROMBOPAG, hederagenin
Interactions	ABCA1, ACAT1, ACETYL-COA, ACHE, ACOD1, ACOX1
SciDEX Target	View Target Profile
SciDEX Hypotheses	Cell-Type Specific TFEB Modulation The Mitochondrial-Lysosomal Metabolic Coupling Dys Radiation drives pericyte senescence through lysos (+4 more)
KG Connections	3007 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

🔮 Predicted Structure: TFEB — AlphaFold Q3KNW5 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (14)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    TFEB["TFEB
(Master Regulator)"]
    
    subgraph Activators["TFEB Activators"]
        TRIM27["TRIM27
(E3 Ligase)"]
        CREB1["CREB1
(Transcription Factor)"]
        trehalose["Trehalose
(Metabolite)"]
        QGJZF["QGJZF"]
    end
    
    subgraph Regulators["Upstream Regulators"]
        MTORC1["mTORC1
(Kinase Complex)"]
        AMBRA1["AMBRA1
(Autophagy Regulator)"]
    end
    
    subgraph TargetGenes["Target Genes/Proteins"]
        LC3["LC3
(Autophagy Marker)"]
        RRAG["RRAG
(Lysosomal Positioning)"]
        BECN1["BECN1
(Autophagy Initiator)"]
    end
    
    subgraph Pathways["Regulated Pathways"]
        autophagy["Autophagy"]
        endocytosis["Endocytosis"]
        lysosomal_biogenesis["Lysosomal Biogenesis"]
        autophagic_pathway["Autophagy-Lysosomal Pathway"]
    end
    
    subgraph Outcomes["Physiological Outcomes"]
        neurodegen["Neurodegenerative Disease
Modulation"]
        alzheimers["Alzheimer's Disease
Treatment"]
    end
    
    TRIM27 -->|"activates"| TFEB
    CREB1 -->|"activates"| TFEB
    trehalose -->|"activates"| TFEB
    QGJZF -->|"activates"| TFEB
    
    MTORC1 -->|"regulates"| TFEB
    AMBRA1 -->|"inhibits"| TFEB
    
    TFEB -->|"regulates"| LC3
    TFEB -->|"regulates"| RRAG
    TFEB -->|"activates"| BECN1
    
    TFEB -->|"activates"| autophagy
    TFEB -->|"promotes"| endocytosis
    TFEB -->|"regulates"| lysosomal_biogenesis
    TFEB -->|"activates"| autophagic_pathway
    
    autophagy -->|"linked to"| neurodegen
    autophagic_pathway -->|"related to"| alzheimers
    TFEB -->|"modulates"| neurodegen
    TFEB -->|"treats"| alzheimers
    
    classDef mainProtein fill:#ff6b6b,stroke:#c92a2a,stroke-width:3px,color:#e0e0e0,font-weight:bold
    classDef protein fill:#4ecdc4,stroke:#1a9b8e,stroke-width:2px,color:#e0e0e0
    classDef pathway fill:#95e1d3,stroke:#38ada9,stroke-width:2px,color:#e0e0e0
    classDef outcome fill:#ffd93d,stroke:#f39c12,stroke-width:2px,color:#e0e0e0
    classDef regulator fill:#a8dadc,stroke:#457b9d,stroke-width:2px,color:#e0e0e0
    
    class TFEB mainProtein
    class TRIM27,CREB1,LC3,RRAG,BECN1,QGJZF,trehalose,MTORC1,AMBRA1 protein
    class autophagy,endocytosis,lysosomal_biogenesis,autophagic_pathway pathway
    class neurodegen,alzheimers outcome
    class Activators,Regulators regulator

Outgoing (1414)

Target	Relation	Type	Str
Als	activates	disease	1.00
AUTOPHAGY	activates	gene	1.00
Als	regulates	disease	1.00
autophagy	activates	pathway	1.00
Autophagy	activates	pathway	1.00
GENES	activates	gene	1.00
lysosome biogenesis	promotes	process	0.95
Endocytosis	upregulates	process	0.95
Tumor	activates	disease	0.95
FAM134B	upregulates	gene	0.95
lysosomal pool regeneration	regulates	process	0.95
MAFLD	regulates	disease	0.95
syncytiotrophoblast formation	promotes	process	0.95
syncytiotrophoblast differentiation	regulates	process	0.95
lysosomal function	activates	process	0.95
mitochondrial function	activates	process	0.95
AUTOPHAGY	regulates	pathway	0.94
autophagy	regulates	process	0.94
diabetic encephalopathy	therapeutic_target	disease	0.93
intestinal permeability	modulates	phenotype	0.92
Autophagosome and Lysosome Biogenesis	upregulates	pathway	0.92
renal tumorigenesis	promotes	process	0.92
NLRP3	promotes	protein	0.92
Lysosomal Activity	upregulates	process	0.90
PPARGC1A	activates	gene	0.90
Lysosomal Biogenesis	regulates	process	0.90
trophoblast differentiation	promotes	process	0.90
autophagy gene activation	mediates	process	0.90
breast cancer	therapeutic_target	disease	0.90
metabolic dysfunction-associated steatohepatitis	protects_against	disease	0.90
NFE2L2	regulates	gene	0.90
SYNB	binds_to	gene	0.90
lysosomal homeostasis	regulates	process	0.90
lysosomal genes	upregulates	pathway	0.90
microglia activation	inhibits	process	0.90
Lysosome Biogenesis	associated_with	process	0.90
tauopathy	therapeutic_target	disease	0.90
Amyloid-Beta Clearance	activates	process	0.90
Lysosome Biogenesis	activates	process	0.90
17β-Estradiol production	modulates	process	0.90
lysosomal biogenesis	regulates	process	0.90
LC3	regulates	protein	0.90
placental hormone secretion	regulates	process	0.90
CYP19A1	associated_with	gene	0.90
Autophagy-Lysosomal Pathway	mediates	pathway	0.90
NLRP3 inflammasome	inhibits	protein	0.90
autophagic flux	regulates	pathway	0.90
endocytosis	associated_with	pathway	0.90
SYNA	binds_to	gene	0.90
Lysosomal Transcripts	upregulates	biomarker	0.90

Incoming (1594)

Source	Relation	Type	Str
TREHALOSE	activates	gene	0.95
TRPML1	activates	protein	0.95
RAPAMYCIN	activates	drug	0.95
TMX2	promotes_nuclear_import_of	protein	0.95
FLCN	inhibits	protein	0.95
trehalose	activates	drug	0.95
Treahalose	activates	compound	0.95
Sulforaphane	activates	compound	0.95
mTOR	phosphorylates	protein	0.95
mTORC1	upstream_of	protein	0.95
Rag-GTPases	inhibits	protein	0.95
Urolithin A	activates	drug	0.95
cGAS-STING	activates	pathway	0.95
TRIP12	ubiquitinates	protein	0.93
h-e3e8407c	targets	hypothesis	0.90
CREB1	activates	protein	0.90
Trehalose	activates	compound	0.90
TRIM27	activates	protein	0.90
Tnea Therapy	activates	drug	0.90
IRISIN	activates	protein	0.90
Qigui Jiangzhi Formula	upregulates	drug	0.90
ROCK1	phosphorylates	gene	0.90
PPP3	phosphorylates	gene	0.90
MTORC1	inhibits	gene	0.90
h-e5a1c16b	targets_gene	hypothesis	0.90
tetrandrine	modulates	compound	0.90
TMX2	modulates	protein	0.90
rapamycin	targets	drug	0.90
PRKAA	activates	gene	0.90
Mc3R Agonists	activates	drug	0.90
h-b9acf0c9	targets	hypothesis	0.90
mTOR inhibition	activates	process	0.90
h-1775578a	targets	hypothesis	0.90
GABARAP	inhibits	protein	0.88
1433	binds_to	protein	0.85
nutrient insufficiency	modulates	process	0.85
Lysosomal-Mediated Activation	regulates	mechanism	0.85
mTORC1	phosphorylates	protein	0.85
MTOR	associated_with	protein	0.85
TSC2	regulates	gene	0.85
STAT3	inhibits	entity	0.85
Acetylation	modulates	mechanism	0.85
ACSS2	binds	protein	0.85
TAL1	regulates	enzyme	0.85
ELTROMBOPAG	inhibits	drug	0.85
PPP2	phosphorylates	protein	0.85
HESPERIDIN	activates	compound	0.85
MC3R	modulates	protein	0.85
TFEB phosphorylation	regulates	mechanism	0.85
Acetylation	regulates	process	0.80

Targeting Hypotheses (22)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TFEB Nuclear Translocation to Reset Lysosomal-Hypoxia Axis	0.779	neurodegeneration	What molecular mechanism causes VCP muta
TFEB/TFE3 Parallel Activation Drives Coordinated Organelle C	0.727	neurodegeneration	How do different organelle-specific auto
TFEB-Independent Autophagy Bypass	0.697	neurodegeneration	Does TFEB dysfunction cause neurodegener
TFEB-Dependent Lysosome Biogenesis	0.690	neurodegeneration	How does controlled lysosomal membrane p
TFEB-mediated transcriptional upregulation of lysosomal gene	0.680	neuroscience	Lysosomal dysfunction and cathepsin leak

Cell-Type Specific TFEB Modulation	0.677	neurodegeneration	Does TFEB dysfunction cause neurodegener
The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction	0.652	neurodegeneration	Metabolic reprogramming in neurodegenera
Radiation drives pericyte senescence through lysosome acidif	0.652	neurodegeneration	What specific autophagy pathways are def
mTORC1 displacement from lysosomal surface enables calcineur	0.650	neurodegeneration	What determines the specificity of calci
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling	0.622	neurodegeneration	Gene expression changes in aging mouse b
Lysosomal pH Restoration Upstream of TFEB	0.619	neurodegeneration	Does TFEB dysfunction cause neurodegener
Temporal TFEB Modulation Therapy	0.609	neurodegeneration	Does TFEB dysfunction cause neurodegener
Selective TFEB Cofactor Enhancement	0.602	neurodegeneration	Does TFEB dysfunction cause neurodegener
PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5	0.584	neurodegeneration	How does PIKFYVE inhibition activate unc
Impaired TFEB/TFE3 Nuclear Translocation Due to mTORC1 Hyper	0.578	neurodegeneration	What mechanisms underlie neuronal resist
Synergistic enhancement of autophagy and lysosomal biogenesi	0.565	neuroscience	Lysosomal dysfunction and cathepsin leak
TFEB Activation Clears Tau-Loaded Endolysosomal Compartments	0.560	neurodegeneration	Investigate prion-like spreading of tau
HBOT (2.0 ATA, 60 min) activates TFEB-mediated autophagy-lys	0.560	neurodegeneration	What are the optimal oxygen pressure, du
YWHAG-Mediated TFEB Subcellular Targeting	0.549	neurodegeneration	Does TFEB dysfunction cause neurodegener
TFEB Activation to Restore Lysosomal Biogenesis in Aged Syna	0.533	proteomics	Quantitative proteomics of the aging syn
TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inf	0.485	Neuroinflammation	Immune atlas neuroinflammation analysis
Parallel Multi-Pathway Convergence on TFEB Activation	0.450	neurodegeneration	Why do structurally diverse sugars (treh

Mentioning Analyses (22)

Scientific analyses that reference this entity

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.583

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

proteomics | 2026-04-16 | 7 hypotheses Top: 0.533

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

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.793

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

neurodegeneration | 2026-04-13 | 2 hypotheses Top: 0.584

What validated biomarkers can determine optimal TFEB activity windows during dis

neurodegeneration | 2026-04-11 | 0 hypotheses

Experiments (8)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Trehalose-induced lysosomal membrane permeabilization and TFEB activat	exploratory	motoneuron degeneration	0.900	NSC34 neuroblastoma cells	proposed	N/A
Trehalose-induced lysosomal changes and TFEB activation	exploratory	motoneuron degeneration	0.900	NSC34 neuroblastoma x spinal c	proposed	N/A
Transcriptome sequencing of cardiac fibroblasts in TFEB overexpressing	exploratory	myocardial infarction	0.900	R26-LSL-TFEB+/+; Acta2-cre mic	proposed	N/A
TFEB silencing and misfolded protein degradation	exploratory	motoneuron degeneration	0.880	NSC34 neuroblastoma x spinal c	proposed	N/A
Protein expression analysis and cell migration assays in cardiac fibro	exploratory	cardiac fibrosis	0.880	primary cardiac fibroblasts fr	proposed	N/A
Functional validation of trehalose effects on misfolded protein cleara	exploratory	motoneuron degeneration diseas	0.850	cell models expressing misfold	proposed	N/A
ChIP-qPCR validation of TFEB binding to Thbs1 promoter	exploratory	cardiac fibrosis	0.850	mouse cardiac fibroblasts	proposed	N/A
Trehalose analog testing for autophagy induction	exploratory	motoneuron degeneration	0.820	NSC34 neuroblastoma x spinal c	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Autophagy and ALS: mechanistic insights and therapeutic implications. [PMID:34057020]	Chua JP, De Calbiac H, Kabashi E, Barmad	Autophagy	2022	2
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of [PMID:30335591]	Rusmini P, Cortese K, Crippa V, Cristofa	Autophagy	2019	2
Acetylation in the regulation of autophagy. [PMID:35435793]	Xu Y, Wan W	Autophagy	2023	1
Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Protein [PMID:41900026]	Jamerlan A, Hulme J	Molecules (Basel, Switzerland)	2026	0
Enhanced lysosomal activity prevents infection with PrPSc and the seeding activi [PMID:41391758]	Mercer RCC, Le NTT, Mirza-Romero NA, Orb	The Journal of biological chem	2026	0
Mammalian lipophagy: process and function. [PMID:41681129]	Zhao R, Dai E, Kang R, Liu J, Klionsky D	Autophagy	2026	0
PSAT1 inhibits mTORC1 activation by preventing Rag heterodimer formation in lung [PMID:40702660]	Liu Y, Cheng Z, Zhang J, Zhang Y, Zhao T	Autophagy	2026	0
Electroacupuncture regulates neuronal ferroptosis and ferritinophagy through lys [PMID:41272418]	Tang B, Xu X, Zhao W, Zhou Q, Du G et al	J Cereb Blood Flow Metab	2026	0
Nanocarrier-enhanced simvastatin modulates AMPK-ULK1 pathway and oxidative stres [PMID:41314452]	Afify AM, El-Sayed EK, Ismail A, Nofal S	Eur J Pharmacol	2026	0
Macrophage PD-1 regulates energy expenditure and metabolic dysfunction under imm [PMID:41380676]	Wu MM, Yang YC, Hu ZQ, Chang JY, Xiao H	Cell Metab	2026	0
Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 [PMID:41400694]	Jacqmin T, Gilis F, Albert M, Gaussin JF	J Cell Biol	2026	0
Endothelial Transcription Factor EB Protects Against Doxorubicin-Induced Endothe [PMID:41410033]	Du W, Ringer M, Desai D, Khandakar GI, T	Circulation	2026	0
Proteotoxic stress triggers TFEB- and TFE3-mediated autophagy and lysosomal biog [PMID:41450115]	Zhu Z, Yang J, Montefusco S, Xia S, Ou J	Autophagy	2026	0
β-Sitosterol ameliorates metabolic dysfunction-associated steatohepatitis by tar [PMID:41501416]	Wang Y, Sun Y, Wang CY, Cao M, Hao R et	Acta Pharmacol Sin	2026	0
Epigenetic H3K4me3 activation of miR-155-5p promotes intervertebral disc degener [PMID:41536620]	Wang X, Sun H, Xiao W, Zhang Y, Lu X et	Noncoding RNA Res	2026	0
AMPK promotes TFEB transcriptional activity through dephosphorylation at both MT [PMID:41661247]	Negoita F, Fraguas Bringas C, Hellberg K	Autophagy	2026	0
Microglia TFEB activation attenuates Alzheimer's disease pathology by enhancing [PMID:41673711]	Kim Y, Ha TY, Kondaurova O, Lee MS, Chan	J Neuroinflammation	2026	0
Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzhe [PMID:41720088]	Luo S, Liu H, Xiao T, Li Y, Liu X et al.	Cell Rep Med	2026	0
Prussian Blue Nanozyme Disrupts the Self-Reinforcing Loop of Tauopathy via Tripl [PMID:41797478]	Wu F, Huang J, Wang J, Wu R, Zhang H et	Adv Healthc Mater	2026	0
SLC38A9 Regulation Affects Hippocampal Neuronal Autophagy: A Potential Alzheimer [PMID:41811103]	Chen Y, Ji X, Zhao J, Bao Z, Huang Y	CNS Neurosci Ther	2026	0

Debates (20)

Multi-agent debates referencing this entity

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

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

Lysosomal membrane permeabilization releasing cathepsins triggers NLRP3 inflamma

closed · Rounds: 4 · Score: 0.76 · 2026-04-22

The study shows trehalose causes lysosomal membrane permeabilization (LMP) that

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

While the study establishes that trehalose-induced lysosomal permeabilization ac

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

The finding that trehalase-resistant analogs and other disaccharides mimic treha

closed · Rounds: 4 · Score: 0.60 · 2026-04-21

The debate identified this as a critical mechanistic gap - TFEB may increase lys

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

The core causation versus correlation debate remains unresolved despite being ce

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

The debate proposed temporal TFEB modulation but identified no validated biomark

closed · Rounds: 4 · Score: 1.00 · 2026-04-20

How does synaptic protein turnover change with age and neurodegeneration, and wh

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

closed · Rounds: 4 · Score: 0.78 · 2026-04-13

Related Research

Hypotheses and analyses mentioning TFEB in their description or question text

Cell-Type Specific TFEB Modulation

Score: 0.677 · neurodegeneration · 2026-04-04

## Mechanistic Overview Cell-Type Specific TFEB Modulation starts from the claim that modulating TFEB within the disease

The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction

Score: 0.652 · neurodegeneration · 2026-04-02

## Mechanistic Overview The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction starts from the claim that modulating

Radiation drives pericyte senescence through lysosome acidification failure and

Score: 0.652 · neurodegeneration · 2026-04-25

Autophagosomes still form after irradiation, but damaged lysosomes cannot clear cargo, sustaining ROS and SASP output.

mTORC1 displacement from lysosomal surface enables calcineurin access to TFEB

Score: 0.650 · neurodegeneration · 2026-04-21

## Mechanistic Overview mTORC1 displacement from lysosomal surface enables calcineurin access to TFEB starts from the cl

TFEB-PGC1α Mitochondrial-Lysosomal Decoupling

Score: 0.622 · neurodegeneration · 2026-04-02

## Mechanistic Overview TFEB-PGC1α Mitochondrial-Lysosomal Decoupling starts from the claim that modulating TFEB within

Lysosomal pH Restoration Upstream of TFEB

Score: 0.619 · neurodegeneration · 2026-04-04

## Mechanistic Overview Lysosomal pH Restoration Upstream of TFEB starts from the claim that modulating ATP6V1A within t

Temporal TFEB Modulation Therapy

Score: 0.609 · neurodegeneration · 2026-04-04

## Mechanistic Overview Temporal TFEB Modulation Therapy starts from the claim that modulating TFEB within the disease c

Selective TFEB Cofactor Enhancement

Score: 0.602 · neurodegeneration · 2026-04-04

## Mechanistic Overview Selective TFEB Cofactor Enhancement starts from the claim that modulating TFE3 within the diseas

PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineur

Score: 0.584 · neurodegeneration · 2026-04-13

## Mechanistic Overview PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineurin→TFEB Cascade

Impaired TFEB/TFE3 Nuclear Translocation Due to mTORC1 Hyperactivity in Motor Ne

Score: 0.578 · neurodegeneration · 2026-04-26

Motor neurons exhibit constitutive mTORC1 activation that phosphorylates TFEB/TFE3 transcription factors, sequestering t

Synergistic enhancement of autophagy and lysosomal biogenesis by combined mTOR i

Score: 0.565 · neuroscience · 2026-04-22

## Mechanistic Overview Synergistic enhancement of autophagy and lysosomal biogenesis by combined mTOR inhibition and TF

TFEB Activation Clears Tau-Loaded Endolysosomal Compartments, Preventing Release

Score: 0.560 · neurodegeneration · 2026-04-22

## Mechanistic Overview TFEB Activation Clears Tau-Loaded Endolysosomal Compartments, Preventing Release for Transcellul

HBOT (2.0 ATA, 60 min) activates TFEB-mediated autophagy-lysosome pathway to acc

Score: 0.560 · neurodegeneration · 2026-04-25

HBOT increases mTORC1 inhibition, promoting TFEB nuclear translocation and enhancing autophagy flux to clear pathologica

YWHAG-Mediated TFEB Subcellular Targeting

Score: 0.549 · neurodegeneration · 2026-04-04

## Mechanistic Overview YWHAG-Mediated TFEB Subcellular Targeting starts from the claim that modulating YWHAG within the

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses

Score: 0.533 · proteomics · 2026-04-25

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses

TFEB

Understanding Entity Pages

Summary

Wiki Pages (14)

Metabolic-Energetic Restoration: GLP-1 + TFEB Activator Combination

Section 244: Advanced Autophagy Induction and TFEB Activation in CBS/PSP

Mitophagy Gate Therapy: PINK1/Parkin + TFEB Priming

TFEB Autophagy Pathway

TFEB Signaling in Neurodegeneration

TFEB-Mediated Lysosomal Biogenesis

TFEB Activators for Parkinson's Disease

TFEB Activators in Neurodegeneration

TFEB Protein (Transcription Factor EB)

TFEB Activator Therapies for Neurodegenerative Diseases

PD TFEB Activator and Lysosomal Biogenesis Companies

TFEB Protein

TFEB

TFEB (Redirect)

Pathway Diagram

Outgoing (1414)

Incoming (1594)

Targeting Hypotheses (22)

Mentioning Analyses (22)

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

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

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

What validated biomarkers can determine optimal TFEB activity windows during dis

Does TFEB activation directly restore mutant GBA enzyme activity or only enhance

Does TFEB dysfunction causally drive neurodegeneration or represent compensatory

Why do structurally diverse sugars (trehalose, melibiose, lactulose) produce ide

What determines the specificity of calcium-dependent PPP3/calcineurin activation

How does controlled lysosomal membrane permeabilization induce autophagy without

Lysosomal dysfunction and cathepsin leakage in Alzheimer disease progression

Tau propagation mechanisms and therapeutic interception points

Does TFEB dysfunction cause neurodegeneration or represent a compensatory respon

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Circuit-level neural dynamics in neurodegeneration

Metabolic reprogramming in neurodegenerative disease

Sleep disruption as cause and consequence of neurodegeneration

Mitochondrial transfer between astrocytes and neurons

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

Mechanistic role of APOE in neurodegeneration

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (8)

Related Papers (20)

Debates (20)

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Lysosomal membrane permeabilization releasing cathepsins triggers NLRP3 inflamma

The study shows trehalose causes lysosomal membrane permeabilization (LMP) that

While the study establishes that trehalose-induced lysosomal permeabilization ac

The finding that trehalase-resistant analogs and other disaccharides mimic treha

The debate identified this as a critical mechanistic gap - TFEB may increase lys

The core causation versus correlation debate remains unresolved despite being ce

The debate proposed temporal TFEB modulation but identified no validated biomark

How does synaptic protein turnover change with age and neurodegeneration, and wh

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

Related Research

Cell-Type Specific TFEB Modulation

The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction

Radiation drives pericyte senescence through lysosome acidification failure and

mTORC1 displacement from lysosomal surface enables calcineurin access to TFEB

TFEB-PGC1α Mitochondrial-Lysosomal Decoupling

Lysosomal pH Restoration Upstream of TFEB

Temporal TFEB Modulation Therapy

Selective TFEB Cofactor Enhancement

PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineur

Impaired TFEB/TFE3 Nuclear Translocation Due to mTORC1 Hyperactivity in Motor Ne

Synergistic enhancement of autophagy and lysosomal biogenesis by combined mTOR i

TFEB Activation Clears Tau-Loaded Endolysosomal Compartments, Preventing Release

HBOT (2.0 ATA, 60 min) activates TFEB-mediated autophagy-lysosome pathway to acc

YWHAG-Mediated TFEB Subcellular Targeting

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses