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

12Experiments

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
GNAL	co_discussed	gene	0.40
OPTN	co_discussed	gene	0.40
OPTINEURIN	co_discussed	protein	0.40
SQSTM1	co_discussed	gene	0.40
P62	co_discussed	protein	0.40
TAX1BP1	co_discussed	gene	0.40
TOLLIP	co_discussed	gene	0.40
UBIQUITIN	co_discussed	protein	0.40
ULK1	co_discussed	gene	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
SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senesc	0.893	neurodegeneration	Gene expression changes in aging mouse b
Optimized Temporal Window for Metabolic Boosting Therapy Det	0.887	neurodegeneration	How do different microglial subtypes (DA
TBK1 Loss Locks Microglia in an Aged/Senescent Transcription	0.878	als	What are the mechanisms by which microgl
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.869	alzheimers	Circuit-level neural dynamics in neurode
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt

Microglial Senescence Prevention via TREM2/SASP Axis	0.837	neurodegeneration	Does the cancer-cystatin-C-TREM2 pathway
TREM2 Deficiency Drives Microglial Senescence via Lipid Meta	0.836	neurodegeneration	What molecular mechanisms drive microgli
Differential Complement Regulator Expression on Synaptic Mem	0.833	synaptic-biology	What determines the selectivity of compl
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna	0.820	alzheimers	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
ω-3 Docosahexaenoic Acid (DHA) Epoxide Generation via CYP2J2	0.802	lipidomics	Lipid metabolism dysregulation in Alzhei
Senescent Microglia Resolution via Maresins-Senolytics Combi	0.791	neurodegeneration	Neuroinflammation resolution mechanisms
Therapeutic Window Exists Because Amplified Signals (Not Bas	0.780	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
Oligodendrocyte Precursor Cell Senescence in White Matter Di	0.769	-	Senescent cell clearance as neurodegener
p21^Cip1 Phospho-State as Autophagy Responsiveness Predictor	0.768	molecular-biology	What is the optimal therapeutic window t
APOE4 Allosteric Rescue via Small Molecule Chaperones	0.765	neurodegeneration	APOE4 structural biology and therapeutic
Repeat-domain exposure defines seed-competent tau conformers	0.760	neurodegeneration	Seed-competent tau conformers in trans-s
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
PD-Associated GWAS Variants in CTSO and CTSF Genes Create a	0.743	neurodegeneration	-
Senescent Cell Mitochondrial DNA Release	0.742	neurodegeneration	Senolytic therapy for age-related neurod
Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determ	0.738	neuroinflammation	How do B cells mechanistically orchestra
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
Regional TREM2-Dependent Lipid Metabolism Determines Cortica	0.721	neuroinflammation	How do regional, age, and sex-dependent
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
TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagatio	0.000	als	What are the mechanisms by which microgl

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (12)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	0.00	human patients	proposed	N/A
Irisin effects on osteogenic differentiation in mesenchymal stem cells	exploratory	bone fracture	0.900	0.00	mouse bone mesenchymal stem ce	proposed	N/A
Spp1 knockout prevents synaptic loss in AD mouse models	validation	Alzheimer's disease	0.900	0.00	Spp1 knockout AD mouse models	proposed	N/A
Synaptic plasticity and protein expression analysis in mPFC	exploratory	insomnia-anxiety comorbidity	0.850	0.00	mPFC brain slices from PCPA-tr	proposed	N/A
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.509	0.50	human postmortem brain tissue	proposed	$520,000
s:** - Test whether HCN1 knockout specifically in EC layer II accelera	falsification	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$80,000
AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Positive Indiv	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
AD Combination Therapy Trial: Anti-Aβ + Anti-Tau	clinical	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$180,000
Animal Model Comparison for Neurodegenerative Disease Therapeutics	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,100,000
Biomarker-Guided Sequential Therapy Selection in Alzheimer's Disease	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
tACS Connectivity Trial in Early Alzheimer's	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.400	0.50	mouse	proposed	$730,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Antidepressant effects of combined eucommia-gastrodia extract via modulation of [PMID:41921863]	Xue L, Pan Z, Liu Y, Gan Q, Liu D, Liu D	Brain research bulletin	2026
Complementary mechanisms of high-carbohydrate diets and ketogenic diets restore [PMID:41475465]	Kwon H, Seo DS, Ahmad Y, Park S, Yoo J,	The Journal of nutritional bio	2026
TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate micr [PMID:41922794]	Shi X, Cai SZ, Chai JL, Xu CY, Zhou BY,	Molecular psychiatry	2026
The Potential Functions and Beneficial Effects of Melatonin on Cognitive Impairm [PMID:41917799]	Li XY, Cheng YZ, Zhang YM, Hu F, Fang SK	Brain and behavior	2026
Biomarkers for Alzheimer's disease across diverse biological domains: an umbrell [PMID:40680830]	Kang J, Son Y, Yim Y, Cho H, Kim J et al	J Adv Res	2026
Nanotherapeutic potential of Baicalein-encapsulated hUC-MSC exosomes in Alzheime [PMID:41370943]	Xu J, He Z, Pan Y, Cao B, Chen G	Biomater Adv	2026
Epigenetic mechanisms and therapeutic innovations in chronic pain-associated neu [PMID:41554641]	Zhang K, Zhu S, Xing N, Zhou Z, Chen J e	Br J Pharmacol	2026
Postbiotics and the gut-brain axis: A mechanistic review on modulating neuroinfl [PMID:41570486]	Lahariya R, Anand G, Kumari B, Priyadars	J Neuroimmunol	2026
miRNA-206 in muscle and central nervous system crosstalk during exercise: A doub [PMID:41571168]	Malvandi AM, Gerosa L, Maroni P, Orlando	Neurosci Biobehav Rev	2026
Experts' narrative review "Mastication, Hippocampal Structure Changes and Cognit [PMID:41576846]	Piancino MG	Arch Oral Biol	2026
Opioid-induced transcriptional reprogramming of cerebrospinal fluid immune cells [PMID:41674808]	Acharya A, Ambikan AT, Neogi U, Lamberty	Res Sq	2026
Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer's dis [PMID:41678917]	Xue D, Hu X, Li R, Sun T, Qian S et al.	Phytomedicine	2026
Siah2 is a lipid-mediated metabolic sensor in adipose tissue macrophage. [PMID:41690475]	Dang TN, Ghosh B, Panta PR, Taylor JM, K	J Lipid Res	2026
Dysregulation of Drp1 and Mfn2 is associated with reduced PSD-95, synaptophysin, [PMID:41932483]	Alfateh M, Vasconcelos C, Choker AH, Moh	Int J Biol Macromol	2026
AICAR improves depression-like behaviors and is associated with hippocampal AMPK [PMID:41932583]	Takahashi K, Kurokawa K, Kawaguchi R, Ta	Neurochem Int	2026
Human umbilical cord mesenchymal stem cells therapy for Alzheimer's disease: a s [PMID:41847685]	Si C, Ma L, Ding W, Tian Y, Zhang J, Cao	Frontiers in neurology	2026
Cannabidiol and pBDNF Cotreatment Attenuates Pathological Symptoms and Improves [PMID:41924980]	Chaulagain B, Gothwal A, Mahanta AK, Jar	ACS chemical neuroscience	2026
Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerati [PMID:41868184]	Liu Z, Zhang H, Wan B, Yin S, Yue R	Drug design, development and t	2026
Modulation of mitochondrial quality by exercise mimetics: A potential strategy f [PMID:41804756]	Ke Z, Wang B, Liang R	Journal of Alzheimer's disease	2026
Neurotransmitter dysregulation in depression, anxiety, and suicidality: From syn [PMID:41924767]	K S V ABG, Verma AK, A SS, Sinha SS, Boy	Psychiatry research	2026

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

Microglial Senescence Prevention via TREM2/SASP Axis

Score: 0.837 · neurodegeneration · 2026-04-17

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

TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation

Score: 0.836 · neurodegeneration · 2026-04-22

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

Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)

Score: 0.833 · synaptic-biology · 2026-04-21

**Molecular Mechanism and Rationale** The differential expression of complement regulators CD55 (decay-accelerating fac

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 · alzheimers · 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

ω-3 Docosahexaenoic Acid (DHA) Epoxide Generation via CYP2J2 to Protect Synaptic

Score: 0.802 · lipidomics · 2026-04-25

The hypothesis proposes that ω-3 docosahexaenoic acid (DHA) is metabolized by CYP2J2 to generate protective epoxides tha

Senescent Microglia Resolution via Maresins-Senolytics Combination

Score: 0.791 · neurodegeneration · 2026-04-02

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

Therapeutic Window Exists Because Amplified Signals (Not Baseline) Drive Pathoge

Score: 0.780 · neurodegeneration · 2026-04-26

G2019S basal RAB10 phosphorylation elevation may be secondary; true pathogenic driver is amplified stress-response signa

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

p21^Cip1 Phospho-State as Autophagy Responsiveness Predictor

Score: 0.768 · molecular-biology · 2026-04-21

**Molecular Mechanism and Rationale** The p21^Cip1 protein, encoded by the CDKN1A gene, functions as a critical molecul

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

Repeat-domain exposure defines seed-competent tau conformers

Score: 0.760 · neurodegeneration · 2026-04-26

Tau assemblies become seed-competent when their repeat-domain surfaces adopt a conformation that both survives transfer

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