protein

NES

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NES: 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.

34Connections

30Hypotheses

0Analyses

12Outgoing

22Incoming

7Experiments

0Debates

Summary

Page for NES Protein

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🔬 Protein Info

Gene Symbol	NES
Molecular Weight	~177 kDa
GeneCards	NES
Human Protein Atlas	NES
Associated Diseases	ALS, dementia, frontotemporal
KG Connections	34 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (2)

Knowledge base pages for this entity

NESTIN: Intermediate Filament Protein in Neural Stem Cells and Neurodegeneration

gene · 1827 words

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NES Protein

protein · 822 words

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Pathway Diagram

graph TD
    NES["NES Protein"]
    AUTOPHAGY["Autophagy Process"]
    ULK1["ULK1 Kinase"]
    BECN1["Beclin-1"]
    P62["p62/SQSTM1"]
    OPTINEURIN["Optineurin"]
    NDP52["NDP52"]
    UBIQUITIN["Ubiquitin"]
    C9ORF72["C9orf72"]
    SMCR8["SMCR8"]
    FUS["FUS Protein"]
    ACTIN["Actin Cytoskeleton"]
    ALS["Amyotrophic Lateral Sclerosis"]
    FTD["Frontotemporal Dementia"]
    TRIM2["TRIM2 E3 Ligase"]

    NES -->|"regulates"| AUTOPHAGY
    ULK1 -->|"initiates"| AUTOPHAGY
    BECN1 -->|"promotes"| AUTOPHAGY
    AUTOPHAGY -->|"degrades"| P62
    AUTOPHAGY -->|"degrades"| OPTINEURIN
    P62 -->|"cargo receptor"| AUTOPHAGY
    OPTINEURIN -->|"selective autophagy"| AUTOPHAGY
    NDP52 -->|"autophagy receptor"| AUTOPHAGY
    UBIQUITIN -->|"tags substrates"| P62
    UBIQUITIN -->|"marks cargo"| OPTINEURIN
    C9ORF72 -->|"forms complex"| SMCR8
    C9ORF72 -->|"regulates"| AUTOPHAGY
    FUS -->|"aggregates in disease"| ALS
    NES -->|"interacts with"| ACTIN
    TRIM2 -->|"ubiquitinates"| NES
    AUTOPHAGY -->|"dysfunction leads to"| ALS
    AUTOPHAGY -->|"dysfunction leads to"| FTD

    style NES fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px
    style AUTOPHAGY fill:#1a3a2a,stroke:#81c784,stroke-width:2px
    style ULK1 fill:#1a3a2a,stroke:#81c784,stroke-width:2px
    style BECN1 fill:#1a3a2a,stroke:#81c784,stroke-width:2px
    style P62 fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style OPTINEURIN fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style NDP52 fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style UBIQUITIN fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style C9ORF72 fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style SMCR8 fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style FUS fill:#3a1a1a,stroke:#ef5350,stroke-width:2px
    style ACTIN fill:#2a1a3a,stroke:#ce93d8,stroke-width:2px
    style ALS fill:#3a2a1a,stroke:#ffa726,stroke-width:2px
    style FTD fill:#3a2a1a,stroke:#ffa726,stroke-width:2px
    style TRIM2 fill:#3a1a1a,stroke:#ef5350,stroke-width:2px

Outgoing (12)

Target	Relation	Type	Str
ALS	associated_with	disease	0.60
dementia	associated_with	disease	0.60
frontotemporal	associated_with	disease	0.60
SQSTM1	co_discussed	gene	0.40
P62	co_discussed	protein	0.40
TAX1BP1	co_discussed	gene	0.40
GNAL	co_discussed	gene	0.40
UBIQUITIN	co_discussed	protein	0.40
ULK1	co_discussed	gene	0.40
TOLLIP	co_discussed	gene	0.40
OPTN	co_discussed	gene	0.40
OPTINEURIN	co_discussed	protein	0.40

Incoming (22)

Source	Relation	Type	Str
CHMP2B	co_expressed_with	gene	0.50
TRIM2	co_discussed	gene	0.40
AUTOPHAGY	co_discussed	process	0.40
LATE	co_discussed	disease	0.40
STING	co_discussed	gene	0.40
ACTB	co_discussed	gene	0.40
ACTIN	co_discussed	protein	0.40
ALS	co_discussed	disease	0.40
AMYOTROPHIC LATERAL SCLEROSIS	co_discussed	gene	0.40
BECN1	co_discussed	gene	0.40
C9ORF72	co_discussed	gene	0.40
SMCR8	co_discussed	gene	0.40
CALCOCO2	co_discussed	gene	0.40
NDP52	co_discussed	gene	0.40
FTD	co_discussed	disease	0.40
DEMENTIA	co_discussed	gene	0.40
FUS	co_discussed	protein	0.40
RNA	co_discussed	gene	0.40
G3BP1	co_discussed	gene	0.40
MAP1LC3	co_discussed	gene	0.40
LC3	co_discussed	protein	0.40
NBR1	co_discussed	gene	0.40

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Metabolic Reprogramming to Reverse Senescence	1.000	-	Senescent cell clearance as neurodegener
TREM2-Dependent Microglial Senescence Transition	0.950	neurodegeneration	Gene expression changes in aging mouse b
CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microgli	0.921	neurodegeneration	Lipid raft composition changes in synapt
Autophagy-Senescence Axis Therapeutic Window	0.921	-	Senescent cell clearance as neurodegener
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence	0.910	neurodegeneration	Gene expression changes in aging mouse b

SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.895	neurodegeneration	Gene expression changes in aging mouse b
Optimized Temporal Window for Metabolic Boosting Therapy Det	0.879	neurodegeneration	How do different microglial subtypes (DA
TREM2-Mediated Cholesterol Dysregulation in Microglial Senes	0.869	neurodegeneration	Gene expression changes in aging mouse b
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
Microglial Senescence Prevention via TREM2/SASP Axis	0.847	neurodegeneration	View
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.831	Alzheimer's disease	Circuit-level neural dynamics in neurode
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	View
Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna	0.820	Alzheimer's disease	Circuit-level neural dynamics in neurode
Extracellular Vesicle Biogenesis Modulation	0.814	neurodegeneration	Tau propagation mechanisms and therapeut
CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-S	0.811	neurodegeneration	What are the cell-type-specific transcri
TREM2 Deficiency Drives Microglial Senescence via Lipid Meta	0.800	neurodegeneration	What molecular mechanisms drive microgli
Senescent Microglia Resolution via Maresins-Senolytics Combi	0.784	neurodegeneration	Neuroinflammation resolution mechanisms
Oligodendrocyte Precursor Cell Senescence in White Matter Di	0.769	-	Senescent cell clearance as neurodegener
APOE4 Allosteric Rescue via Small Molecule Chaperones	0.765	neurodegeneration	APOE4 structural biology and therapeutic
Senescence-Activated NAD+ Depletion Rescue	0.755	neurodegeneration	Senolytic therapy for age-related neurod
TREM2-SIRT1 Metabolic Senescence Circuit in Microglial Aging	0.744	neurodegeneration	Gene expression changes in aging mouse b
Senescent Cell Mitochondrial DNA Release	0.742	neurodegeneration	Senolytic therapy for age-related neurod
Senescence-Associated Myelin Lipid Remodeling	0.732	neurodegeneration	Senolytic therapy for age-related neurod
Senescence-Induced Lipid Peroxidation Spreading	0.730	neurodegeneration	Senolytic therapy for age-related neurod
Differential Complement Regulator Expression on Synaptic Mem	0.725	synaptic biology	What determines the selectivity of compl
ω-3 Docosahexaenoic Acid (DHA) Epoxide Generation via CYP2J2	0.725	lipidomics	Lipid metabolism dysregulation in Alzhei
APOE4-driven pericyte injury/senescence is an upstream drive	0.720	neurodegeneration	Does pericyte senescence drive BBB break
H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astroc	0.720	neurodegeneration	Do APOE4-driven senescent astrocytes cau
NLRP3 Inflammasome Lock Perpetuates Senescence-Associated In	0.720	neurodegeneration	What molecular mechanisms drive microgli
TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR	0.718	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (7)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	human patients	proposed	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	Mouse (5xFAD/TREM2-/-)	completed	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	Mouse (5xFAD/TREM2-/-)	completed	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	Mouse (5xFAD/TREM2-/-)	in_progress	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	Mouse (5xFAD/TREM2-/-)	completed	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	Mouse (5xFAD/TREM2-/-)	completed	N/A
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.200	Mouse (5xFAD/TREM2-/-)	in_progress	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Ca [PMID:35642214]	Wang M, Pan W, Xu Y, Zhang J, Wan J, Jia	J Inflamm Res	2022	1
TREM2, microglia, and Alzheimer's disease. [PMID:33516818]	Qin Q, Teng Z, Liu C, Li Q, Yin Y, Tang	Mech Ageing Dev	2021	1
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease. [PMID:28802038]	Ulland TK, Song WM, Huang SC, Ulrich JD,	Cell	2017	1
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Mic [PMID:28930663]	Krasemann S, Madore C, Cialic R, Baufeld	Immunity	2017	1
Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and T [PMID:41833042]	["Lyu G", "Li D"]	CNS & neurological disorders d	2026	0
Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuro [PMID:41858793]	["Wang R", "Feng Y", "Zhou Z", "Jiang J"	Frontiers in aging neuroscienc	2026	0
Human CSF proteogenomics links genetic variation to neurodegenerative disease pr [PMID:41757182]	["Puerta R", "Garc\u00eda-Gonz\u00e1lez	medRxiv : the preprint server	2026	0
PLCG2 signaling and genetic resilience in Alzheimer's disease. [PMID:41888907]	Tsai AP, Martin AK, Mi A, Yeh AE, Ramire	Molecular neurodegeneration	2026	0
PLCG2 signaling and genetic resilience in Alzheimer's disease. [PMID:41888907]	Tsai AP, Martin AK, Mi A, Yeh AE, Ramire	Mol Neurodegener	2026	0
TREM2 deficiency delays postnatal microglial maturation and synaptic pruning, le [PMID:41930604]	Yang HC, Deng YS, Zhang J, Zhang T, Song	J Alzheimers Dis	2026	0
Investigating the Potential of Gene Editing Technologies in Enhancing Stem Cell [PMID:41926312]	["Mehrabadi S"]	Current aging science	2026	0
TREM2 in neurodegeneration and diseases. [PMID:41792456]	["Abdulkhaliq A", "Alasiri G", "Kim B",	Molecular psychiatry	2026	0
Berbamine hydrochloride as a brain penetrant galectin 3 inhibitor in a model of [PMID:41772384]	["Siew J", "Lee C", "Chen H", "Lin H", "	Brain : a journal of neurology	2026	0
The microglial TREM2 receptor programs hippocampal development in a mouse model [PMID:41887542]	Ahmed S, Bowers C, Munoz-Martin J, Jamwa	Brain, behavior, and immunity	2026	0
Molecular mechanism of Alzheimer's disease using integrated multi-omics. [PMID:41907842]	Alhusaini M, Mussa BM, Ilce BY, Alhaj H,	Frontiers in aging neuroscienc	2026	0
Oligodendrocyte precursor cells-microglia crosstalk via BMP4 drives microglial n [PMID:41881962]	Baek S, Jang J, Yeo S, Jung HJ, Choe Y	Signal transduction and target	2026	0
Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ4 [PMID:41770935]	["Konstantoulea K", "Ramakers M", "Borri	Proceedings of the National Ac	2026	0
Microglia, Trem2, and Neurodegeneration. [PMID:38769824]	Shi Q, Gutierrez RA, Bhat MA	Neuroscientist	2025	0
Microglia, Trem2, and Neurodegeneration. [PMID:38769824]	Shi Q, Gutierrez RA, Bhat MA	The Neuroscientist : a review	2025	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning NES in their description or question text

SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence

Score: 0.895 · neurodegeneration · 2026-04-12

## Mechanistic Overview SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence starts from the claim that modu

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

Score: 0.879 · neurodegeneration · 2026-04-16

## Mechanistic Overview Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State

TREM2-Mediated Cholesterol Dysregulation in Microglial Senescence

Score: 0.869 · neurodegeneration · 2026-04-07

## Mechanistic Overview TREM2-Mediated Cholesterol Dysregulation in Microglial Senescence starts from the claim that mod

Senescent Cell ASM-Complement Cascade Intervention

Score: 0.852 · neurodegeneration · 2026-04-07

## Mechanistic Overview Senescent Cell ASM-Complement Cascade Intervention starts from the claim that modulating SMPD1 w

Microglial Senescence Prevention via TREM2/SASP Axis

Score: 0.847 · neurodegeneration · 2026-04-17

## Mechanistic Overview Microglial Senescence Prevention via TREM2/SASP Axis starts from the claim that modulating not y

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhyth

Score: 0.831 · Alzheimer's disease · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and bl

SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via

Score: 0.824 · neurodegeneration · 2026-04-17

## Mechanistic Overview SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Depen

Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation

Score: 0.820 · Alzheimer's disease · 2026-04-02

## Mechanistic Overview Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation starts from the cl

Extracellular Vesicle Biogenesis Modulation

Score: 0.814 · neurodegeneration · 2026-04-16

## Mechanistic Overview Extracellular Vesicle Biogenesis Modulation starts from the claim that modulating CHMP4B within

CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerabilit

Score: 0.811 · neurodegeneration · 2026-04-16

## Mechanistic Overview CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerability Thresholds sta

TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation

Score: 0.800 · neurodegeneration · 2026-04-22

## Mechanistic Overview TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation starts from the

Senescent Microglia Resolution via Maresins-Senolytics Combination

Score: 0.784 · neurodegeneration · 2026-04-02

## Mechanistic Overview Senescent Microglia Resolution via Maresins-Senolytics Combination starts from the claim that mo

Oligodendrocyte Precursor Cell Senescence in White Matter Disease

Score: 0.769 · unknown disease · 2026-04-16

## Mechanistic Overview Oligodendrocyte Precursor Cell Senescence in White Matter Disease starts from the claim that mod

APOE4 Allosteric Rescue via Small Molecule Chaperones

Score: 0.765 · neurodegeneration · 2026-04-02

## Mechanistic Overview APOE4 Allosteric Rescue via Small Molecule Chaperones starts from the claim that modulating APOE

Senescence-Activated NAD+ Depletion Rescue

Score: 0.755 · neurodegeneration · 2026-04-02

## Mechanistic Overview Senescence-Activated NAD+ Depletion Rescue starts from the claim that modulating CD38/NAMPT with