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.

3094Connections

30Hypotheses

30Analyses

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
Associated Diseases	aging, Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	Ampk Activators, bortezomib, curcumin, CURCUMIN, digoxin, ELTROMBOPAG
Interactions	14-3-3, ABCA1, ACAT1, ACETYL-COA, ACHE, ACOD1
SciDEX Target	View Target Profile
SciDEX Hypotheses	GBA1 Loss Triggers a TFEB-to-TFE3 Compensatory Swi Cell-Type Specific TFEB Modulation The Mitochondrial-Lysosomal Metabolic Coupling Dys (+17 more)
KG Connections	3092 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 (1485)

Target	Relation	Type	Str
TFEB	encodes	protein	0.00
Als	activates	disease	1.00
autophagy	activates	pathway	1.00
Autophagy	activates	pathway	1.00
AUTOPHAGY	activates	gene	1.00
Als	regulates	disease	1.00
GENES	activates	gene	1.00
syncytiotrophoblast formation	promotes	process	0.95
FAM134B	upregulates	gene	0.95
lysosomal function	activates	process	0.95
lysosomal pool regeneration	regulates	process	0.95
Tumor	activates	disease	0.95
mitochondrial function	activates	process	0.95
syncytiotrophoblast differentiation	regulates	process	0.95
lysosome biogenesis	promotes	process	0.95
Endocytosis	upregulates	process	0.95
MAFLD	regulates	disease	0.95
AUTOPHAGY	regulates	pathway	0.94
autophagy	regulates	process	0.94
diabetic encephalopathy	therapeutic_target	disease	0.93
NLRP3	promotes	protein	0.92
intestinal permeability	modulates	phenotype	0.92
Autophagosome and Lysosome Biogenesis	upregulates	pathway	0.92
renal tumorigenesis	promotes	process	0.92
Lysosomal Transcripts	upregulates	biomarker	0.90
lysosomal biogenesis	activates	process	0.90
autophagic flux	regulates	pathway	0.90
Lysosome Biogenesis	activates	process	0.90
Autophagy	mediates	process	0.90
autophagy_pathway	activates	pathway	0.90
lysosomal biogenesis	regulates	process	0.90
NFE2L2	regulates	gene	0.90
endocytosis	associated_with	pathway	0.90
lysosomal_function	regulates	phenotype	0.90
LC3	regulates	protein	0.90
metabolic dysfunction-associated steatohepatitis	protects_against	disease	0.90
lysosomal_biogenesis	regulates	phenotype	0.90
mitophagy	promotes	process	0.90
autophagy gene transcription	regulates	process	0.90
placental hormone secretion	regulates	process	0.90
NLRP3 inflammasome	inhibits	protein	0.90
lysosomal homeostasis	regulates	process	0.90
SYNA	binds_to	gene	0.90
tauopathy	therapeutic_target	disease	0.90
microglia activation	inhibits	process	0.90
lysosomal genes	upregulates	pathway	0.90
SYNB	binds_to	gene	0.90
Mitochondrial Function	regulates	process	0.90
Autophagy Gene Expression	regulates	gene	0.90
17β-Estradiol production	modulates	process	0.90

Incoming (1609)

Source	Relation	Type	Str
TFEB	encodes	gene	0.00
TRPML1	activates	protein	0.95
mTOR	phosphorylates	protein	0.95
Sulforaphane	activates	compound	0.95
RAPAMYCIN	activates	drug	0.95
trehalose	activates	drug	0.95
cGAS-STING	activates	pathway	0.95
Treahalose	activates	compound	0.95
FLCN	inhibits	protein	0.95
TMX2	promotes_nuclear_import_of	protein	0.95
TREHALOSE	activates	gene	0.95
Urolithin A	activates	drug	0.95
mTORC1	upstream_of	protein	0.95
Rag-GTPases	inhibits	protein	0.95
TRIP12	ubiquitinates	protein	0.93
TMX2	modulates	protein	0.90
rapamycin	activates	drug	0.90
IRISIN	activates	protein	0.90
rapamycin	targets	drug	0.90
CREB1	activates	protein	0.90
PRKAA	activates	gene	0.90
TRIM27	activates	protein	0.90
ROCK1	phosphorylates	gene	0.90
MTORC1	inhibits	gene	0.90
Trehalose	activates	compound	0.90
Mtorc1	phosphorylates	protein	0.90
mTOR inhibition	activates	process	0.90
Mc3R Agonists	activates	drug	0.90
PPP3	phosphorylates	gene	0.90
mTOR	inhibits	gene	0.90
GSK-3β inhibitors	activates	drug	0.90
Qigui Jiangzhi Formula	upregulates	drug	0.90
Tnea Therapy	activates	drug	0.90
h-1775578a	targets	hypothesis	0.90
tetrandrine	modulates	compound	0.90
14-3-3	inhibits	protein	0.90
h-e5a1c16b	targets_gene	hypothesis	0.90
h-b9acf0c9	targets	hypothesis	0.90
h-e3e8407c	targets	hypothesis	0.90
GABARAP	inhibits	protein	0.88
MTOR	associated_with	protein	0.85
HESPERIDIN	activates	compound	0.85
TFEB phosphorylation	regulates	mechanism	0.85
ELTROMBOPAG	inhibits	drug	0.85
STAT3	inhibits	entity	0.85
TAL1	regulates	enzyme	0.85
PPP2	phosphorylates	protein	0.85
ACSS2	binds	protein	0.85
TSC2	regulates	gene	0.85
nutrient insufficiency	modulates	process	0.85

Targeting Hypotheses (30)

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
GBA1 Loss Triggers a TFEB-to-TFE3 Compensatory Switch in A9	0.750	neurodegeneration	-
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	0.679	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
SNCA Oligomers Sequester TFEB Phosphatases to Create a Phosp	0.650	neurodegeneration	-
mTORC1 Displacement from Lysosomal Membrane Enables TFEB Nuc	0.640	neurodegeneration	-
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
Impaired TFEB/TFE3 Nuclear Translocation Due to mTORC1 Hyper	0.603	neurodegeneration	What mechanisms underlie neuronal resist
Selective TFEB Cofactor Enhancement	0.602	neurodegeneration	Does TFEB dysfunction cause neurodegener
TFEB Activation to Restore Lysosomal Biogenesis in Aged Syna	0.591	proteomics	Quantitative proteomics of the aging syn
PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5	0.584	neurodegeneration	How does PIKFYVE inhibition activate unc
TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-	0.580	neurodegeneration	Test Preregistration Analysis
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
TFEB-Mediated Lysosomal Biogenesis Restoration for GRN Haplo	0.560	neurodegeneration	Test
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 Alzheimer	0.523	proteomics	Quantitative proteomics of the aging syn
TFEB-Mediated Retromer Biogenesis to Restore Endosomal-Lysos	0.510	proteomics	Quantitative proteomics of the aging syn
TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inf	0.485	neuroinflammation	Immune atlas neuroinflammation analysis
LAMP1 Overexpression to Enhance Lysosomal Capacity Independe	0.000	proteomics	Quantitative proteomics of the aging syn
Cell-Type-Specific TFEB Modulation Combined with Trehalose f	0.000	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (30)

Scientific analyses that reference this entity

Microglial senescence in Alzheimer and Parkinson disease progression

neurodegeneration | 2026-04-26 | 0 hypotheses

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

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

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

neurodegeneration | 2026-04-25 | 12 hypotheses Top: 0.640

What specific autophagy pathways are defective in radiation-induced pericyte sen

neurodegeneration | 2026-04-25 | 3 hypotheses Top: 0.652

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

proteomics | 2026-04-16 | 19 hypotheses Top: 0.591

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

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

closed · Rounds: 4 · Score: 0.65 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

closed · Rounds: 4 · Score: 0.71 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

closed · Rounds: 4 · Score: 0.87 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

closed · Rounds: 4 · Score: 0.48 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II somatostatin interneurons to restore de

closed · Rounds: 4 · Score: 0.54 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound with real-time gamma feedbac

closed · Rounds: 4 · Score: 0.19 · 2026-04-27

Hypothesis debate: Closed-loop transcranial alternating current stimulation to r

closed · Rounds: 4 · Score: 0.40 · 2026-04-27

Hypothesis debate: Closed-loop transcranial focused ultrasound to restore hippoc

closed · Rounds: 4 · Score: 0.50 · 2026-04-27

Related Research

Hypotheses and analyses mentioning TFEB in their description or question text

TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic s

Score: 0.679 · neuroscience · 2026-04-22

**Molecular Mechanism and Rationale** The transcription factor EB (TFEB) represents a master regulatory node in cellula

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

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

Score: 0.603 · neurodegeneration · 2026-04-26

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

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

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses

Score: 0.591 · proteomics · 2026-04-25

TFEB (together with TFE3 and TFEB family members) is a master transcriptional regulator of lysosomal biogenesis and auto

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

TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-Lysosome Pathway

Score: 0.580 · neurodegeneration · 2026-04-28

Forced nuclear localization of TFEB using AAV9-TFEB(S211A) induces transcription of autophagy-lysosomal genes, enhancing

TFEB

Understanding Entity Pages

Summary

Wiki Pages (14)

TFEB Protein (Transcription Factor EB)

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 Activator Therapies for Neurodegenerative Diseases

PD TFEB Activator and Lysosomal Biogenesis Companies

TFEB Protein

TFEB

TFEB (Redirect)

Pathway Diagram

Outgoing (1485)

Incoming (1609)

Targeting Hypotheses (30)

Mentioning Analyses (30)

Microglial senescence in Alzheimer and Parkinson disease progression

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

What specific autophagy pathways are defective in radiation-induced pericyte sen

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

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

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

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

How does PIKFYVE inhibition activate unconventional protein clearance via exocyt

Do SCFAs directly modulate α-synuclein aggregation in vivo at physiologically re

Do P2RX7 antagonists selectively block pathogenic exosomes while preserving bene

What validated biomarkers can determine optimal TFEB activity windows during dis

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

Do tau strains or regional cellular environments primarily drive PSP vs CBD path

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 do different organelle-specific autophagy pathways coordinate during neurode

How does APOE4 mechanistically increase TDP-43 pathology frequency in Alzheimer'

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

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

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

Experiments (8)

Related Papers (20)

Debates (20)

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

Debate: Closed-loop tACS targeting EC-II somatostatin interneurons to restore de

Debate: Closed-loop transcranial focused ultrasound with real-time gamma feedbac

Hypothesis debate: Closed-loop transcranial alternating current stimulation to r

Hypothesis debate: Closed-loop transcranial focused ultrasound to restore hippoc

Related Research

TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic s

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

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

Selective TFEB Cofactor Enhancement

TFEB Activation to Restore Lysosomal Biogenesis in Aged Synapses

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

TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-Lysosome Pathway