concept

AUTOPHAGY-LYSOSOME PATHWAY

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AUTOPHAGY-LYSOSOME PATHWAY: 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.

44Connections

8Hypotheses

3Analyses

26Outgoing

18Incoming

19Experiments

4Debates

No summary available yet.

View on Wiki →

No AI portrait yet

💡 Concept Info

Name	AUTOPHAGY-LYSOSOME PATHWAY
Key Genes/Proteins	AMPK, C9orf72, NLRP3, SQSTM1, TARDBP, TBK1
Related Diseases	AMYOTROPHIC LATERAL SCLEROSIS, AUTOPHAGY, DEMENTIA, FRONTOTEMPORAL DEMENTIA, MITOPHAGY

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Autophagy-Lysosome Pathway in Neurodegeneration

mechanism · 2348 words

→

Pathway Diagram

graph TD
    AUTOPHAGY_LYSOSOME_PATHWAY["AUTOPHAGY-LYSOSOME PATHWAY"]
    AUTOPHAGY_LYSOSOME_PATHWAY -->|"degrades"| NLRP3["NLRP3"]
    AUTOPHAGY_LYSOSOME_PATHWAY -->|"degrades"| SCIN["SCIN"]
    AUTOPHAGY_LYSOSOME_PATHWAY -->|"involved_in"| Glucocorticoid_Induced_Muscle_["Glucocorticoid-Induced Muscle Atrophy"]
    AUTOPHAGY_LYSOSOME_PATHWAY -->|"regulates"| alpha_synuclein["alpha-synuclein"]
    Schaftoside["Schaftoside"] -->|"activates"| AUTOPHAGY_LYSOSOME_PATHWAY
    extracellular_matrix_remodelin["extracellular matrix remodeling"] -->|"enhances"| AUTOPHAGY_LYSOSOME_PATHWAY
    CAMK2D["CAMK2D"] -->|"regulates"| AUTOPHAGY_LYSOSOME_PATHWAY
    ASTROCYTE["ASTROCYTE"] -->|"regulates"| AUTOPHAGY_LYSOSOME_PATHWAY
    Obestatin["Obestatin"] -->|"regulates"| AUTOPHAGY_LYSOSOME_PATHWAY
    MTOR["MTOR"] -->|"regulates"| AUTOPHAGY_LYSOSOME_PATHWAY
    mTOR["mTOR"] -->|"regulates"| AUTOPHAGY_LYSOSOME_PATHWAY
    alpha_synuclein -->|"inhibits"| AUTOPHAGY_LYSOSOME_PATHWAY

Outgoing (26)

Target	Relation	Type	Str
NLRP3	degrades	protein	0.90
TDP-43 Aggregation	involved_in	mechanism	0.85
SCIN	degrades	protein	0.85
Glucocorticoid-Induced Muscle Atrophy	involved_in	disease	0.80
NLRP3	regulates	protein	0.70
alpha-synuclein	regulates	protein	0.70
Parkinson's disease	associated_with	disease	0.70
proteostasis network	modulates	process	0.70
proteostasis	regulates	process	0.70
TDP-43	associated_with	protein	0.45
SQSTM1	associated_with	gene	0.45
TARDBP	associated_with	gene	0.45
NEURON	associated_with	cell_type	0.45
MITOPHAGY	associated_with	phenotype	0.45
TFEB	associated_with	gene	0.45
ULK1	associated_with	gene	0.45
TBK1	associated_with	gene	0.45
AMPK	associated_with	gene	0.45
FRONTOTEMPORAL DEMENTIA	associated_with	disease	0.45
RAPAMYCIN	associated_with	drug	0.45
DEMENTIA	associated_with	disease	0.45
AUTOPHAGY	associated_with	phenotype	0.45
MICROGLIA	associated_with	cell_type	0.45
NLRP3	associated_with	gene	0.45
UBIQUITIN	associated_with	protein	0.45
C9orf72	associated_with	gene	0.45

Incoming (18)

Source	Relation	Type	Str
TDP-43	inhibits	protein	0.90
lnc-HIBADH-4/miR-326/CTSD	regulates	pathway	0.90
extracellular matrix remodeling	enhances	process	0.90
Schaftoside	activates	compound	0.90
35000546	are degraded by	paper	0.90
OBST	regulates	protein	0.85
CAMK2D	regulates	protein	0.85
Obestatin	regulates	compound	0.80
C9ORF72	dysregulates	gene	0.80
Rapamycin	activates	drug	0.80
ASTROCYTE	regulates	cell_type	0.80
mTOR	regulates	protein	0.70
alpha-synuclein	inhibits	protein	0.70
MTOR	regulates	protein	0.70
FOXO1	participates_in	gene	0.62
VCP	participates_in	gene	0.49
STX17	participates_in	gene	0.47
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	disease	0.45

Targeting Hypotheses (8)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Transcriptional Autophagy-Lysosome Coupling	0.757	neurodegeneration	Autophagy-lysosome pathway convergence a
Early Proteasome Restoration Therapy	0.712	neurodegeneration	Gene expression changes in aging mouse b
Autophagosome Maturation Checkpoint Control	0.709	neurodegeneration	Autophagy-lysosome pathway convergence a
VCP-Mediated Autophagy Enhancement	0.595	Alzheimer's Disease	Tau propagation mechanisms and therapeut
TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-	0.580	neurodegeneration	Test Preregistration Analysis

HBOT (2.0 ATA, 60 min) activates TFEB-mediated autophagy-lys	0.560	neurodegeneration	What are the optimal oxygen pressure, du
CHIP-mediated K63-linked ubiquitination promotes autophagoso	0.380	protein biochemistry	Do chaperones selectively recognize path
TFEB-mediated Autophagy Enhancement to Clear Protein Aggrega	0.380	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (3)

Scientific analyses that reference this entity

Why have numerous phase 3 clinical trials failed despite advances in understandi

neurodegeneration | 2026-04-12 | 1 hypotheses Top: 0.566

Tau propagation mechanisms and therapeutic interception points

neurodegeneration | 2026-04-04 | 15 hypotheses Top: 0.814

Autophagy-lysosome pathway convergence across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.757

Experiments (19)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Meta-analysis of LRP1 C766T polymorphism and Alzheimer's disease susce	exploratory	Alzheimer's disease	0.950	0.00	human patients	proposed	N/A
Endothelial CD2AP knockdown effects on memory in male mice	validation	Alzheimer's disease	0.900	0.00	male mice	proposed	N/A
Amyloid plaque load analysis in triple-mutant mouse brains	exploratory	Alzheimer's disease	0.880	0.00	APP/PSEN1/GD3S-/- triple-trans	proposed	N/A
Reelin treatment rescue via ApoER2 in CD2AP mutant mice	validation	Alzheimer's disease	0.870	0.00	mice	proposed	N/A
Network Pharmacology Analysis of Shared AD Targets	exploratory	Alzheimer's disease	0.850	0.00	Computational network analysis	proposed	N/A
MRI Phenotyping Method Concordance in Serbian AD Cohort	clinical	Alzheimer's disease	0.850	0.00	human patients	proposed	N/A
Endothelin-1 receptor A antagonist rescue in male CD2AP mice	validation	Alzheimer's disease	0.850	0.00	male mice	proposed	N/A
Endothelin-1 receptor A antagonist rescue experiment	validation	Alzheimer's disease	0.850	0.00	mice	proposed	N/A
Neuroimmune modulation and Aβ clearance mechanisms	exploratory	Alzheimer's disease	0.820	0.00	Microglia and astrocytes	proposed	N/A
Competing endogenous RNA (ceRNA) network construction	exploratory	Alzheimer's disease	0.750	0.00	computational network analysis	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
ER-Golgi Secretory Pathway Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000

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
Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteost [PMID:40868276]	Voicu V, Toader C, Șerban M, Covache-Bus	Biomedicines	2025	1
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
Acetylation in the regulation of autophagy. [PMID:35435793]	Xu Y, Wan W	Autophagy	2023	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
New insights regarding SNARE proteins in autophagosome-lysosome fusion. [PMID:32924745]	Tian X, Teng J, Chen J	Autophagy	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
Autophagosomes form at ER-mitochondria contact sites. [PMID:23455425]	Hamasaki M, Furuta N, Matsuda A, Nezu A,	Nature	2013	1
Gut Microbiota-Derived Tyrosol Alleviates Radiation-Induced Intestinal Injury vi [PMID:41800257]	Jin X, Xue H, Shi X, Zhou Y, Zhang J, Ze	International journal of biolo	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
SNX16 functions as a nutrient-sensitive regulator of autophagosomal components r [PMID:41593027]	Que H, Rong Y	Autophagy	2026	0
TMEM259/MEMBRALIN is a non-canonical ER-phagy receptor that associates with MAN1 [PMID:41799849]	Camilleri JM, Zhang J, Wang T, Ahmad I,	Autophagy reports	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
Unveiling the Genomic Landscape of Yan Goose (Anser cygnoides): Insights into Po [PMID:41594384]	Qi S, Ai Z, Cai Y, Zhang Y, Zhao W et al	Animals (Basel)	2026	0
Combining network pharmacology and multi-omics reveals the role of Shengdihuang- [PMID:41655545]	Cao X, Shang Y, Qu M, Kang Q, Xu Y et al	Phytomedicine	2026	0
Comparative transcriptomics of adherent and suspension chicken fibroblast cell l [PMID:41763754]	Contreras EJ, Nagarajan A, Bromberg BH,	Food Res Int	2026	0

Debates (4)

Multi-agent debates referencing this entity

Why have numerous phase 3 clinical trials failed despite advances in understandi

closed · Rounds: 5 · Score: 0.67 · 2026-04-12

Investigate prion-like spreading of tau pathology through connected brain region

closed · Rounds: 4 · Score: 0.90 · 2026-04-12

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

Tau propagation mechanisms and therapeutic interception points

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

Related Research

Hypotheses and analyses mentioning AUTOPHAGY-LYSOSOME PATHWAY in their description or question text

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

CHIP-mediated K63-linked ubiquitination promotes autophagosomal sequestration of

Score: 0.380 · protein biochemistry · 2026-04-27

The carboxy terminus of Hsc70-interacting protein (CHIP, encoded by STUB1) functions as a dual-specificity E3 ubiquitin

TFEB-mediated Autophagy Enhancement to Clear Protein Aggregates in Neurodegenera

Score: 0.380 · proteomics · 2026-04-27

This hypothesis proposes that TFEB activation serves as a therapeutic strategy for neurodegenerative diseases by enhanci