enzyme

PROTEASOME

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about PROTEASOME: 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.

947Connections

4Hypotheses

0Analyses

50Outgoing

50Incoming

0Experiments

0Debates

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🔬 Protein Info

Gene Symbol	PROTEASOME
Function	[@emmanouilidis2021], [@mcgann2022], [@xiong2019]
Pathways	APOPTOSIS, AUTOPHAGY, Cerebrovascular, Chaperone, FERROPTOSIS
GeneCards	PROTEASOME
Human Protein Atlas	PROTEASOME
Catalytic subunit impairment	26S proteasome activity declines 20-40% by age 70
Assembly defects	PA700 complex formation becomes inefficient
Oxidative modification	Age-related oxidative stress damages proteasome subunits
Inhibitory accumulation	Aggregated proteins inhibit proteasome activity
Subunit composition changes	α-subunit expression decreases while β-subunits remain stable
Direct inhibition	Oligomeric alpha-synuclein binds to and inhibits 20S proteasome catalytic core
Ubiquitination interference	Pathological alpha-synuclein disrupts E3 ligase function
Sequestration	UPS components are recruited to Lewy bodies, depleting functional pool
Feed-forward loop	UPS impairment allows more alpha-synuclein to accumulate
Aggregate spreading	Proteasome dysfunction enables templated propagation of α-syn aggregates
Associated Diseases	MULTIPLE SCLEROSIS, disease
Interactions	SNCA, SQSTM1, TAU
KG Connections	11 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

proteasome-ubiquitin-system-dysfunction-parkinsons

general · 3977 words

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Pathway Diagram

graph TD
    PROTEASOME["PROTEASOME"] -->|"modulates"| HDAC6["HDAC6"]
    style HDAC6 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| UBIQUITIN["UBIQUITIN"]
    style UBIQUITIN fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"associated"| AUTOPHAGY["AUTOPHAGY"]
    style AUTOPHAGY fill:#1a2a3a,stroke:#ffd54f,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| NEURON["NEURON"]
    style NEURON fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"interacts"| P62["P62"]
    style P62 fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"regulates"| BECN1["BECN1"]
    style BECN1 fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| LYSOSOME["LYSOSOME"]
    style LYSOSOME fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    TAU["TAU"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style TAU fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    SNCA["SNCA"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style SNCA fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    SQSTM1["SQSTM1"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style SQSTM1 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    NRF2["NRF2"] -->|"regulates"| PROTEASOME["PROTEASOME"]
    style NRF2 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    AUTOPHAGY_1["AUTOPHAGY"] -->|"associated"| PROTEASOME["PROTEASOME"]
    style AUTOPHAGY_1 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style PROTEASOME fill:#006494,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0,font-weight:bold

Outgoing (86)

Target	Relation	Type	Str
TNF	regulates	protein	0.90
TAU	degrades	protein	0.85
TNF-α mRNA stability	regulates	phenotype	0.80
TTP	modifies	protein	0.80
Fibrosis	therapeutic_target	disease	0.60
Ferroptosis	degrades	disease	0.60
Als	contributes_to	disease	0.60
Dementia	activates	disease	0.60
Als	activates	disease	0.60
Alzheimer	contributes_to	disease	0.60
Als	inhibits	disease	0.60
Ischemia	inhibits	disease	0.60
Cancer	activates	disease	0.60
Alzheimer	regulates	disease	0.60
Als	therapeutic_target	disease	0.60
Parkinson	therapeutic_target	disease	0.60
Diabetes	regulates	disease	0.60
Atherosclerosis	regulates	disease	0.60
Parkinson	activates	disease	0.60
Aging	expressed_in	disease	0.60
Cancer	expressed_in	disease	0.60
Aging	degrades	disease	0.60
Ischemia	associated_with	disease	0.60
Als	interacts_with	disease	0.60
Aging	activates	disease	0.60
Stroke	activates	disease	0.60
Parkinson	transports	disease	0.60
Alzheimer	transports	disease	0.60
Parkinson	associated_with	disease	0.60
Neurodegeneration	associated_with	disease	0.60
Prion Disease	regulates	disease	0.60
Parkinson	regulates	disease	0.60
Aging	interacts_with	disease	0.60
Amyotrophic Lateral Sclerosis	degrades	disease	0.60
Parkinson	degrades	disease	0.60
Neurodegeneration	degrades	disease	0.60
Alzheimer	degrades	disease	0.60
Ferroptosis	causes	disease	0.60
Neurodegeneration	causes	disease	0.60
Aging	inhibits	disease	0.60
Alzheimer	inhibits	disease	0.60
Cancer	therapeutic_target	disease	0.60
Neurodegeneration	therapeutic_target	disease	0.60
Als	expressed_in	disease	0.60
Huntington	transports	disease	0.60
Blood-Brain Barrier	activates	pathway	0.55
Complement	interacts_with	pathway	0.55
Dna Methylation	expressed_in	pathway	0.55
Glycolysis	causes	pathway	0.55
Autophagy	protects_against	pathway	0.55

Incoming (861)

Source	Relation	Type	Str
UBIQUITIN	regulates	gene	1.00
PARKINSON'S DISEASE	therapeutic_target	gene	1.00
NEURODEGENERATION	activates	gene	1.00
UBIQUITIN	therapeutic_target	gene	1.00
Cancer	therapeutic_target	disease	1.00
UBIQUITIN	associated_with	gene	1.00
UBIQUITIN	inhibits	gene	1.00
PARKINSON	therapeutic_target	gene	1.00
Tumor	therapeutic_target	disease	1.00
UBIQUITIN	activates	gene	1.00
AUTOPHAGY	activates	gene	1.00
NEURODEGENERATION	therapeutic_target	gene	1.00
AUTOPHAGY	regulates	gene	1.00
Neurodegeneration	activates	disease	1.00
Als	activates	disease	1.00
Als	regulates	disease	1.00
NEURODEGENERATION	associated_with	gene	1.00
AUTOPHAGY	associated_with	gene	1.00
Parkinson	therapeutic_target	disease	1.00
Als	therapeutic_target	disease	1.00
Neurodegeneration	therapeutic_target	disease	1.00
Als	inhibits	disease	1.00
CANCER	therapeutic_target	gene	1.00
P53	therapeutic_target	gene	1.00
Neurodegeneration	associated_with	disease	1.00
AUTOPHAGY	therapeutic_target	gene	1.00
GENES	activates	gene	1.00
LYSOSOME	activates	gene	1.00
P62	activates	gene	1.00
Aging	therapeutic_target	disease	1.00
Als	associated_with	disease	0.95
UCH37	associated_with	enzyme	0.95
UBIQUITIN	binds_to	protein	0.90
Neurodegeneration	causes	disease	0.90
Aging	activates	disease	0.90
NEURODEGENERATION	regulates	gene	0.90
NEURODEGENERATION	causes	gene	0.90
APOPTOSIS	therapeutic_target	gene	0.90
CANCER	inhibits	gene	0.90
SQSTM1	activates	gene	0.90
Cancer	regulates	disease	0.85
SQSTM1	associated_with	entity	0.85
NEURON	expressed_in	cell_type	0.85
TAU	associated_with	entity	0.85
SNCA	interacts_with	protein	0.85
SQSTM1	interacts_with	protein	0.85
TAU	interacts_with	protein	0.85
NRF2	regulates	entity	0.80
AUTOPHAGY	associated_with	entity	0.80
GENES	therapeutic_target	gene	0.80

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
proteasome shuttle failure defines the therapeutic window fo	0.723	neurodegeneration	How do ALS-linked UBQLN2 mutations affec
VCP/p97 ATPase mutations impair extraction of ubiquitinated	0.720	neurodegeneration	What are the neuron-specific effects of
Early Proteasome Restoration Therapy	0.712	neurodegeneration	Gene expression changes in aging mouse b
Chaperone-Degradation Coupling Prevents Aggregate Persistenc	0.620	protein folding	Can chaperone enhancement approaches ove

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (0)

Experimental studies targeting or related to this entity

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

Related Papers (10)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
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
NAD+ restores proteostasis through splicing-dependent autophagy. [PMID:41313318]	Ai R, Fang EF	Autophagy	2026
CHIP and aging: a key regulator of proteostasis and cellular senescence. [PMID:40323531]	Unknown	Biogerontology	2025
Proteostasis and autophagy disruption by the aging-related VGVAPG hexapeptide - [PMID:40348194]	Unknown	Neurochemistry international	2025
A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregase [PMID:35517053]	Unknown	Frontiers in aging neuroscienc	2022
Deciphering the Link Between ER<sup>UPR</sup> Signaling and MicroRNA in Pathogen [PMID:35615589]	Unknown	Frontiers in aging neuroscienc	2022
How autophagy can restore proteostasis defects in multiple diseases? [PMID:32043639]	Unknown	Medicinal research reviews	2021
LRSAM1 E3 ubiquitin ligase promotes proteasomal clearance of E6-AP protein. [PMID:33207262]	Unknown	Cellular signalling	2021
Amyloid toxicity in a Drosophila Alzheimer's model is ameliorated by autophagy a [PMID:34062489]	Unknown	Neurobiology of aging	2021
Clearance of the mutant androgen receptor in motoneuronal models of spinal and b [PMID:23810450]	Unknown	Neurobiology of aging	2014

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning PROTEASOME in their description or question text

No additional research found