gene

NFL

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NFL: 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.

309Connections

30Hypotheses

8Analyses

50Outgoing

50Incoming

5Experiments

10Debates

Summary

NFL is a gene implicated in neurodegeneration research. Key relationships include: biomarker for, associated with, therapeutic target. Associated with ALS, Aging, Als. Connected to 169 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	NEFL
Full Name	Neurofilament Light Polypeptide
Chromosome	8p21.2
Protein Family	Intermediate filament family
Function	is a neuronal intermediate filament protein encoded by the NEFL gene on chromosome 8p21.
Primary Expression	CNS and PNS neurons (axons)
Molecular Weight	~61.5 kDa
Amino Acids	543 aa
Exons	4
Pathways	Amyloid, ubiquitin-proteasome
UniProt ID	P07196
NCBI Gene ID	4747
Ensembl ID	ENSG00000104825
OMIM	162280
GeneCards	NEFL
Human Protein Atlas	NEFL
Associated Diseases	Aging, Als, Alzheimer, Amyotrophic Lateral Sclerosis, Dementia
Interactions	ALZHEIMER, ALZHEIMER'S DISEASE, AMYLOID, AMYOTROPHIC LATERAL SCLEROSIS, AND, APOE
KG Connections	275 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: NFL — AlphaFold P07196 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    NFL["NFL"]
    NFL -.biomarker for.-> Neurodegeneration["Neurodegeneration"]
    NFL -.biomarker for.-> Neuroinflammation["Neuroinflammation"]
    NFL -.biomarker for.-> Inflammation["Inflammation"]
    NFL -.biomarker for.-> Als["Als"]
    NFL -.biomarker for.-> Aging["Aging"]
    NFL -.biomarker for.-> Alzheimer["Alzheimer"]
    NFL -->|"target for"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    NFL -->|"target for"| Ms["Ms"]
    UCHL1["UCHL1"] -->|"interacts"| NFL
    GFAP["GFAP"] -->|"interacts"| NFL
    TMEM119["TMEM119"] -->|"interacts"| NFL
    SYNAPTOPHYSIN["SYNAPTOPHYSIN"] -.biomarker for.-> NFL
    BACE1["BACE1"] -.biomarker for.-> NFL
    SOD1["SOD1"] -.protects against.-> NFL
    APOE4["APOE4"] -->|"activates"| NFL
    ALS["ALS"] -.biomarker for.-> NFL
    AMYOTROPHIC_LATERAL_SCLEROSIS["AMYOTROPHIC LATERAL SCLEROSIS"] -->|"target for"| NFL
    NEURODEGENERATIVE_DISEASES["NEURODEGENERATIVE DISEASES"] -.biomarker for.-> NFL

Outgoing (200)

Target	Relation	Type	Str
axonal_integrity	reflects_recovery_of	process	0.00
Alzheimer	biomarker_for	disease	1.00
Als	biomarker_for	disease	1.00
Dementia	biomarker_for	disease	1.00
ALZHEIMER'S DISEASE	biomarker_for	gene	1.00
Neurodegeneration	biomarker_for	disease	0.95
ALS	biomarker_for	disease	0.95
Neuro-Axonal Injury	biomarker_for	process	0.95
Neurodegeneration	biomarker_for	process	0.95
ALS	biomarker_for	disease	0.95
Als	associated_with	disease	0.95
axonal degeneration	biomarker_for	process	0.90
treatment response	biomarker_for	phenotype	0.90
Neurodegeneration	biomarker_for	process	0.90
Amyotrophic Lateral Sclerosis	associated_with	disease	0.90
Multiple Sclerosis	associated_with	disease	0.90
Survival	correlates_with	phenotype	0.90
Neurological Conditions	associated_with	disease	0.90
AD, ALS, FTD	biomarker_for	disease	0.90
neuroaxonal injury	biomarker_for	process	0.90
Amyotrophic Lateral Sclerosis	biomarker_for	disease	0.90
Alsfrs-R Rate Of Decline	correlates_with	phenotype	0.90
BBB permeability-augmented neurodegeneration	biomarker_for	disease	0.90
GFAP	biomarker_for	gene	0.90
DEMENTIA	biomarker_for	gene	0.90
Functional Decline	associated_with	phenotype	0.85
Neuronal Injury	biomarker_for	mechanism	0.85
Encals Predictor Score	modulates	biomarker	0.85
Aging	biomarker_for	disease	0.85
Aging	associated_with	disease	0.85
Functional Decline	biomarker_for	phenotype	0.85
Als Trial Stratified Randomisation	involved_in	process	0.80
Als Trial Enrichment	involved_in	process	0.80
Amyotrophic Lateral Sclerosis	therapeutic_target	disease	0.75
Neuropathy	associated_with	disease	0.75
Als	activates	disease	0.75
Inflammation	associated_with	disease	0.75
Neuroinflammation	biomarker_for	disease	0.75
Alzheimer	associated_with	disease	0.75
Neurodegeneration	associated_with	disease	0.75
ALZHEIMER'S DISEASE	associated_with	gene	0.70
AD progression	biomarker_for	phenotype	0.70
oxidative stress response	participates_in	pathway	0.70
Neurodegeneration	indicates	mechanism	0.70
neurodegeneration	biomarker_for	disease	0.70
NEUROINFLAMMATION	biomarker_for	gene	0.70
Rapid Disease Progression	biomarker_for	phenotype	0.70
GFAP	associated_with	gene	0.70
Amyotrophic Lateral Sclerosis	activates	disease	0.65
Alzheimer	activates	disease	0.65

Incoming (109)

Source	Relation	Type	Str
ALZHEIMER	biomarker_for	gene	1.00
TAU	biomarker_for	gene	1.00
39249107	was the best predictor of	paper	0.90
ALZHEIMER'S DISEASE	associated_with	gene	0.90
damaged neurons	releases	cell_type	0.90
QAlb	associated_with	biomarker	0.90
AMYLOID	biomarker_for	gene	0.90
Quanterix Simoa	correlates_with	biomarker	0.85
Roche Elecsys	correlates_with	biomarker	0.85
Fujirebio Lumipulse	correlates_with	biomarker	0.85
Siemens Healthineers Atellica Im	correlates_with	biomarker	0.85
ALS	biomarker_for	gene	0.80
NEURODEGENERATION	biomarker_for	gene	0.80
NEURODEGENERATION	associated_with	gene	0.74
TAU	associated_with	gene	0.74
TAU PATHOLOGY	biomarker_for	gene	0.70
ALZHEIMER	associated_with	gene	0.70
GFAP	interacts_with	gene	0.60
C9ORF72	inhibits	gene	0.60
GRN	inhibits	gene	0.60
GAIN	therapeutic_target	gene	0.60
FUS	therapeutic_target	gene	0.60
MAX	therapeutic_target	gene	0.60
DES	biomarker_for	gene	0.60
MICROGLIA	biomarker_for	gene	0.60
UCHL1	interacts_with	gene	0.60
NEURODEGENERATIVE DISEASES	activates	gene	0.60
30283395	elevated in	paper	0.60
APOE Ε4 ALLELE	associated_with	gene	0.60
BRAIN INJURY	causes	gene	0.60
TMEM119	interacts_with	gene	0.60
TMEM106B	interacts_with	gene	0.60
NEUROGRANIN	biomarker_for	gene	0.60
UBIQUITIN	biomarker_for	gene	0.60
MAPT	inhibits	gene	0.60
APOE4	activates	gene	0.60
SOD1	protects_against	gene	0.60
SOD1	associated_with	gene	0.60
GR	expressed_in	gene	0.60
GR	causes	gene	0.60
BACE1	biomarker_for	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	therapeutic_target	gene	0.60
ALZHEIMER'S DISEASE	biomarker_for	gene	0.60
AMYLOID-BETA	associated_with	gene	0.60
SLEEP-WAKE CYCLE	biomarker_for	gene	0.60
ASTROCYTES	biomarker_for	gene	0.60
SYNAPTOPHYSIN	biomarker_for	gene	0.60
AND	activates	gene	0.60
NEURODEGENERATIVE DISEASES	biomarker_for	gene	0.60
ALZHEIMER DISEASE	biomarker_for	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Plasma NfL Elevation Secondary to BBB-Associated Transport D	0.940	-	What blood-brain barrier permeability ch
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.824	neurodegeneration	What are the mechanisms by which gut mic
Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-S	0.822	neurodegeneration	What are the mechanisms by which gut mic
Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone	0.808	neurodegeneration	What are the precise temporal dynamics o
Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in N	0.805	neurodegeneration	What are the mechanisms by which gut mic

Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Re	0.804	neurodegeneration	What are the mechanisms by which gut mic
Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neu	0.803	neurodegeneration	What are the mechanisms by which gut mic
NLRP3 inflammasome amplification across AD and PD proteinopa	0.800	multi	Cross-disease neurodegeneration mechanis
Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflam	0.789	neurodegeneration	What are the mechanisms by which gut mic
NLRP3 Inhibition (H7): Downstream Inflammatory Reversal	0.780	neurodegeneration	Does restoring neuronal AMPK activity re
PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocyte	0.779	neuroinflammation	How do oligodendrocytes initiate neuroin
SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resil	0.778	neurodegeneration	Gut Microbiome Analysis in Parkinson's D
Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory Pathway	0.772	neurodegeneration	Which specific factors in conditioned me
GRN/progranulin lysosomal insufficiency across FTD, ALS-spec	0.756	multi	Cross-disease neurodegeneration mechanis
Metabolic Inflexibility Precedes Transcriptional Reprogrammi	0.735	neurodegeneration	What is the optimal therapeutic window f
NLRP3 Inflammasome Inhibition for Neuroprotection in Parkins	0.720	neurodegeneration	Test
NLRP3 Inflammasome Lock Perpetuates Senescence-Associated In	0.720	neurodegeneration	What molecular mechanisms drive microgli
Microglia-Mediated Neuroinflammation as a Disease-Amplifying	0.720	neurodegeneration	Cross-disease neurodegeneration mechanis
Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Pha	0.714	alzheimers	TREM2 agonism vs antagonism in DAM micro
Microglial Disease-Associated States: TREM2-Independent Path	0.710	neurodegeneration	Cell type vulnerability debate in Alzhei
TREM2-APOE4 Axis Drives Metabolic Inflexibility in DAM	0.708	alzheimers	-
TLR4/MyD88/NF-κB Axis Blockade to Interrupt LPS-Mediated Gut	0.703	neurodegeneration	How do gut microbiome-derived metabolite
TREM2 haploinsufficiency dysregulates microglial synaptic su	0.700	neurodegeneration	Synaptic pruning by microglia in neurode
H5: BET Bromodomain Readers Sense Aberrant Chromatin and Dri	0.690	neurodegeneration	Investigate mechanisms of epigenetic rep
Loss of AQP4 Polarization Impairs Glymphatic Perivascular In	0.690	neurodegeneration	What are the specific molecular mechanis
AQP4 Dysregulation Promotes Neuroinflammation Through Impair	0.680	neurodegeneration	What are the specific molecular mechanis
Microglial NOX2 establishes an inflammatory ROS propagation	0.680	neurodegeneration	What mechanisms drive the self-amplifyin
Glial Neuroinflammatory Amplification by TDP-43 Pathology	0.680	neurodegeneration	What mechanisms underlie TDP-43's contri
Microglial TREM2 state determines whether C1q-tagged substra	0.670	neurodegeneration	Does C1q function differ based on subcel
Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain A	0.669	neurodegeneration	What are the mechanisms by which gut mic

Mentioning Analyses (8)

Scientific analyses that reference this entity

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.585

What blood-brain barrier permeability changes serve as early biomarkers for neur

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.940

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

neurodegeneration | 2026-04-26 | 5 hypotheses Top: 0.712

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

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

Multi-modal Biomarker Panel Design for Early AD Detection

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.579

Experiments (5)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Resveratrol protection against renal I/R injury in diabetic rats	validation	diabetic nephropathy	0.900	streptozotocin-induced diabeti	proposed	N/A
TLR expression analysis in Parkinson's disease patients	clinical	Parkinson's disease	0.850	human patients	proposed	N/A
Resveratrol effects on HK-2 cells under hypoxia/reoxygenation	exploratory	diabetic nephropathy	0.850	HK-2 cells cultured in high gl	proposed	N/A
TLR4 Activation Assay with NETs and Anti-CarP Antibodies	exploratory	rheumatoid arthritis	0.850	HEK293 TLR4 reporter cells	proposed	N/A
TLR expression in α-synuclein overexpressing mice	validation	Parkinson's disease	0.800	mice overexpressing human α-sy	proposed	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
Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiqui [PMID:30966861]	["Han X", "Sun S", "Sun Y", "Song Q", "Z	Autophagy	2020	1
Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PK [PMID:40659086]	Li Z, Tan D, Lin J, Zhang T, Liu B et al	J Adv Res	2026	0
Celastrol treatment attenuates the inflammatory response in Alzheimer's disease [PMID:40762111]	Cao F, Zhang P, Zheng Z, Wang P, Wang Y	Neurol Res	2026	0
CircCramp1l targets the miR-532-3p/HMGB1/Drp1 axis to regulate allergic rhinitis [PMID:41519399]	Zhang Y, Wang J, Song Y, Chai J, Li L et	Biochem Pharmacol	2026	0
Neuronal TLR4 upregulation activates the cGAS-STING pathway to induce ferroptosi [PMID:41702081]	Qin H, Yang L, Du J, Xu X, Chen Z et al.	Int Immunopharmacol	2026	0
2'-Fucosyllactose Alleviates Metabolic Hypertension in Mice via Gut Microbiota M [PMID:41926238]	Chen J, Liang S, Liu D, Yang S, Yan Q et	J Agric Food Chem	2026	0
Leveraging intraperitoneal delivery of toll-like receptor agonists to treat peri [PMID:41926324]	Yan H, Chia D, Ernst S, Demuytere J, Cos	Expert Opin Drug Deliv	2026	0
Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses [PMID:41927877]	Miao J, Wang J, Zhou W, Guo J	Sci Rep	2026	0
Anti-carbamylated protein antibodies stabilize carbamylated Histone H3 to promot [PMID:41930627]	Nakabo S, Hanata N, Patino-Martinez E, H	Arthritis Rheumatol	2026	0
In silico design of a novel multi-epitope mRNA vaccine candidate for BtHKU5-CoV- [PMID:41931545]	Zheng N, Xu Y	PLoS Negl Trop Dis	2026	0
Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF. [PMID:41931597]	Ma B, Lyu W, Rizk J, Han X, Kjær M et al	Sci Immunol	2026	0
Interweaving microglial senescence and gut microbiome dynamics in Alzheimer's di [PMID:41747877]	Waghmare A, Rahangdale S, Khare K, Taksa	Molecular and cellular neurosc	2026	0
Nanopiezoelectric 3D-Bioprinted Neural Organoid Models Epileptic Neuron-Microgli [PMID:41877549]	Chu J, Hu K, Lee WF, Xu SJ, Sun Z, Xu Y,	Nano letters	2026	0
The Neuroameliorative Effects of Enzymatically Modified Isoquercitrin and Sodium [PMID:41880086]	Hassouna I, Hassanein OH, El-Elaimy IA,	Neurochemical research	2026	0
Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An [PMID:41870813]	Upadhayay S	Molecular neurobiology	2026	0
Hyperglycaemia-induced metabolic stress and epigenetic imprinting in the inflamm [PMID:41730508]	Razi FB, Ashraf H, Singhal S, Qamar Z, M	Diabetes research and clinical	2026	0
Colonic Barrier Dysfunction and Inflammation Induced by Nano-/Micro-Plastics Fib [PMID:41923296]	Li Y, Bao S, Huang P, Wang J, Li H, Liu	Journal of applied toxicology	2026	0
Artemisinin attenuates 3-nitropropionic acid-induced neurodegeneration via HMGB1 [PMID:41865324]	Mustafa AM, Mudhafar M, Elgindy AM, Esma	Archives of pharmacal research	2026	0
Curcumin and Glycyrrhiza glabra Synergistically Attenuate Alzheimer's Pathology [PMID:41920384]	Liu S, Yan J, Dong J	Neurochemical research	2026	0

Debates (10)

Multi-agent debates referencing this entity

What is the evidence that blood-brain barrier (BBB) permeability changes serve a

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

What blood-brain barrier permeability changes serve as early biomarkers for neur

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

closed · Rounds: 7 · Score: 0.50 · 2026-04-26

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

completed · Rounds: 5 · Score: 0.50 · 2026-04-25

The debate highlighted that most promising targets (VAMP2, ESCRT, fascin-1) are

closed · Rounds: 4 · Score: 0.75 · 2026-04-22

Can a multi-modal biomarker panel combining plasma proteins, neuroimaging featur

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

Should clinical practice adopt multi-modal biomarker panels now, or wait for sin

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

The debate framework identified synaptic vesicle protein modifications as critic

closed · Rounds: 4 · Score: 0.73 · 2026-04-16

Which metabolic biomarkers can distinguish therapeutic response from disease pro

closed · Rounds: 4 · Score: 0.77 · 2026-04-12

Related Research

Hypotheses and analyses mentioning NFL in their description or question text

NFL

Understanding Entity Pages

Summary

Wiki Pages (3)

NEFL Gene

Neurofilament Light Chain (NFL)

INFLAMMATION

Pathway Diagram

Outgoing (200)

Incoming (109)

Targeting Hypotheses (30)

Mentioning Analyses (8)

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

What blood-brain barrier permeability changes serve as early biomarkers for neur

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Multi-modal Biomarker Panel Design for Early AD Detection

What are the specific PTM changes in synaptic vesicle proteins during early AD p

What is the therapeutic window between tau propagation inhibition and essential

Which metabolic biomarkers can distinguish therapeutic response from disease pro

Experiments (5)

Related Papers (20)

Debates (10)

What is the evidence that blood-brain barrier (BBB) permeability changes serve a

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

What blood-brain barrier permeability changes serve as early biomarkers for neur

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

The debate highlighted that most promising targets (VAMP2, ESCRT, fascin-1) are

Can a multi-modal biomarker panel combining plasma proteins, neuroimaging featur

Should clinical practice adopt multi-modal biomarker panels now, or wait for sin

The debate framework identified synaptic vesicle protein modifications as critic

Which metabolic biomarkers can distinguish therapeutic response from disease pro

Related Research

Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for

Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neurodegeneration

NLRP3 inflammasome amplification across AD and PD proteinopathy

Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory Priming

NLRP3 Inhibition (H7): Downstream Inflammatory Reversal

PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes

SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microb

Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory Pathway

GRN/progranulin lysosomal insufficiency across FTD, ALS-spectrum stress, and AD

Metabolic Inflexibility Precedes Transcriptional Reprogramming (NAD+/SIRT3 Axis)

NLRP3 Inflammasome Inhibition for Neuroprotection in Parkinson's Disease

NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome Phenotype

Microglia-Mediated Neuroinflammation as a Disease-Amplifying Mechanism

Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from Infla

Microglial Disease-Associated States: TREM2-Independent Pathways Driving Neuroin