concept

NAD+

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NAD+: 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.

25Connections

12Hypotheses

3Analyses

9Outgoing

16Incoming

7Experiments

4Debates

No summary available yet.

View on Wiki →

No AI portrait yet

💡 Concept Info

Name	NAD+
Key Genes/Proteins	AMPK, CD38, CX43, PARP1, SIRT1
Related Pathways	Cellular Processes
Linked Hypotheses	16 hypotheses

Wiki Pages (11)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    NAD_["NAD+"]
    NAD_ -.protects against.-> Blood_Brain_Barrier_Damage["Blood-Brain Barrier Damage"]
    NAD_ -->|"involved_in"| Purinergic_Signaling["Purinergic Signaling"]
    NAD_ -->|"involved_in"| Redox_Metabolism["Redox Metabolism"]
    NAD_ -->|"involved_in"| DNA_Repair["DNA Repair"]
    NAD_ -->|"regulates"| SIRTUINS["SIRTUINS"]
    NAD_ -->|"regulates"| PARP["PARP"]
    NAD_ -->|"regulates"| CD38["CD38"]
    NAD_ -->|"involved_in"| Energy_Metabolism["Energy Metabolism"]
    Nmn["Nmn"] -->|"contributes to"| NAD_
    NAMPT["NAMPT"] -->|"modulates"| NAD_
    Aging["Aging"] -->|"downregulates"| NAD_
    NMN["NMN"] -->|"involved_in"| NAD_
    AMPK["AMPK"] -->|"activates"| NAD_
    SIRT["SIRT"] -->|"substrate_of"| NAD_
    PARP -->|"downregulates"| NAD_

Outgoing (9)

Target	Relation	Type	Str
h-da9af6a77a	targeted_by	hypothesis	1.00
h-7210c29bb9	targeted_by	hypothesis	1.00
PARP	regulates	enzyme	0.95
SIRT1	modulates	protein	0.90
SIRT1	activates	protein	0.90
BLOOD-BRAIN BARRIER DAMAGE	protects_against	entity	0.90
Cellular Processes	associated_with	biological_process	0.80
SIRT1	regulates	entity	0.70
inflammation	modulates	process	0.70

Incoming (16)

Source	Relation	Type	Str
h-7210c29bb9	targets	hypothesis	1.00
h-da9af6a77a	targets	hypothesis	1.00
Aging	downregulates	process	0.95
Nmn	contributes_to	compound	0.95
31812486	is involved in	paper	0.90
31812486	promotes healthy ageing through regulation of	paper	0.90
35479740	is an orally bioavailable precursor of	paper	0.90
35479740	is ultimately converted to	paper	0.90
35479740	serves as substrate for	paper	0.90
35479740	is converted to	paper	0.90
CX43	regulates	gene	0.80
PARP1	regulates	gene	0.80
AMPK	contributes_to	protein	0.80
PARP	degrades	enzyme	0.80
SIRT	degrades	enzyme	0.80
CD38	depletes	gene	0.50

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
PARP1-NAD+-AIF bioenergetic collapse drives a self-amplifyin	0.760	neurodegeneration	What mechanisms drive the self-amplifyin
Senescence-Activated NAD+ Depletion Rescue	0.755	neurodegeneration	Senolytic therapy for age-related neurod
Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Ove	0.745	neurodegeneration	Epigenetic reprogramming in aging neuron
Metabolic Inflexibility Precedes Transcriptional Reprogrammi	0.735	neurodegeneration	What is the optimal therapeutic window f
NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogram	0.700	neurodegeneration	What molecular mechanisms drive microgli

SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-D	0.698	neurodegeneration	What is the molecular mechanism by which
Mitochondrial NAD+ Salvage Enhancement	0.639	neurodegeneration	Gene expression changes in aging mouse b
NAMPT-Centered NAD+ Restoration to Reverse Basal Forebrain C	0.616	neurodegeneration	Do β-amyloid plaques and neurofibrillary
SIRT6-NAD+ Axis Enhancement Therapy	0.612	neurodegeneration	Epigenetic clocks and biological aging i
NAD+/SARM1 Axis Provides Metabolic Feedback Coupling Mitopha	0.578	neurodegeneration	How do different organelle-specific auto
CD38 Inhibition for NAD+ Restoration and Microglial Senescen	0.575	neurodegeneration	Microglial subtypes in neurodegeneration
NAD+ Precursor Supplementation to Reverse Poly(ADP-ribose) P	0.520	metabolomics	Metabolomic signatures of neurodegenerat

Mentioning Analyses (3)

Scientific analyses that reference this entity

Microglial subtypes in neurodegeneration — friend vs foe

neurodegeneration | 2026-04-17 | 7 hypotheses Top: 0.685

Investigate mechanisms of epigenetic reprogramming in aging neurons

neurodegeneration | 2026-04-10 | 0 hypotheses

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

neurodegeneration | 2026-04-04 | 0 hypotheses

Experiments (7)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Microglial Aging and Immune Memory in Neurodegeneration — Training the	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,960,000
Normal Aging to Alzheimer's Disease Transition Trigger — Identifying t	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,280,000
Peroxisomal Dysfunction Validation in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Senolytic Therapy (D+Q) Phase IIa Trial in Early Alzheimer's Disease	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Sirtuin Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Sirtuin Pathway Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and De [PMID:38580317]	Velma GR, Krider IS, Alves ETM, Courey J	J Med Chem	2024	1
SIRT6-regulated macrophage efferocytosis epigenetically controls inflammation re [PMID:36593966]	Li B, Xin Z, Gao S, Li Y, Guo S, Fu Y, X	Theranostics	2023	1
Assessing the Status of Mandatory Tuberculosis Case Notification among Private P [PMID:35068738]	Duggal K, Elsy M, Majella MG, Akkilagunt	Indian J Community Med	2021	1
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic [PMID:33888596]	Yoshino M, Yoshino J, Kayser BD, Patti G	Science	2021	1
NAD(+) metabolism, stemness, the immune response, and cancer. [PMID:33384409]	Navas LE, Carnero A	Signal Transduct Target Ther	2021	1
Protocol for the Bottom-Up Proteomic Analysis of Mouse Spleen. [PMID:33377090]	Dowling P, Gargan S, Zweyer M, Henry M,	STAR Protoc	2020	1
Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity [PMID:30193097]	Latorre-Muro P, Baeza J, Armstrong EA, H	Mol Cell	2018	1
NAD metabolism fuels human and mouse intestinal inflammation. [PMID:28877980]	Gerner RR, Klepsch V, Macheiner S, Arnha	Gut	2018	1
The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcin [PMID:28329682]	Nargund AM, Pham CG, Dong Y, Wang PI, Os	Cell Rep	2017	1
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype [PMID:26686024]	Wiley CD, Velarde MC, Lecot P, Liu S, Sa	Cell Metab	2016	1
NAD+ and sirtuins in aging and disease. [PMID:24786309]	Imai S, Guarente L	Trends Cell Biol	2014	1
Mitochondrial NAD(+)-mediated mitophagy alleviates type I interferon response to [PMID:41231107]	Lan T, Shang D, Lin L, Wang H, Zou J et	Autophagy	2026	0
SIRT6 inhibits intermittent hypoxia-induced lung injury by stabilizing NRF2. [PMID:41478020]	Qin R, Liu Z, Li R, Li Y, Yang Y et al.	Tissue Cell	2026	0
cGAS-STING signaling in Alzheimer's disease: Microglial mechanisms and therapeut [PMID:41481960]	Fazal F, Dar NJ, Ahamad S, Khan S, Bano	Mol Aspects Med	2026	0
Opportunities and challenges of targeting cGAS-STING in cancer. [PMID:41486397]	Lu C, Wang W, Fu YX	Nat Rev Cancer	2026	0
CircZBTB44-Encoded Peptide ZBTB44-342aa Alleviates Aortic Valve Calcification Vi [PMID:41487094]	Hu D, Lin Y, Huang H, Xian G, Chen Y et	Circ Res	2026	0
Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling a [PMID:41495200]	Li D, Cui G, Yang K, Lu C, Jiang Y et al	Nat Cell Biol	2026	0
cGAS-STING activation in Parkinson's Disease: From mechanisms to Disease-Modifyi [PMID:41500413]	Solomon J, Mandal S, Aran KR	Gene	2026	0
Ubiquitination-directed cytosolic DNA degradation governs cGAS-STING-mediated im [PMID:41512867]	Li L, Ye Q, Ma J, Wang Z, Liu T et al.	Cancer Cell	2026	0
Inflammation-targeted single-atom nanozymes drive microglial depolarization and [PMID:41624511]	Liu B, Xiang C, Zhang X, Guo W, Wu H et	Mater Today Bio	2026	0

Debates (4)

Multi-agent debates referencing this entity

Investigate mechanisms of epigenetic reprogramming in aging neurons [TARGET_ART

closed · Rounds: 0 · Score: 0.50 · 2026-04-21

Investigate mechanisms of epigenetic reprogramming in aging neurons

closed · Rounds: 0 · Score: 0.56 · 2026-04-21

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Related Research

Hypotheses and analyses mentioning NAD+ in their description or question text

SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-Dependent Axon Degene

Score: 0.698 · neurodegeneration · 2026-04-14

## Mechanistic Overview SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-Dependent Axon Degeneration starts fr

Mitochondrial NAD+ Salvage Enhancement

Score: 0.639 · neurodegeneration · 2026-04-04

## Mechanistic Overview Mitochondrial NAD+ Salvage Enhancement starts from the claim that modulating STING1 within the d

NAMPT-Centered NAD+ Restoration to Reverse Basal Forebrain Cholinergic Neuron Me

Score: 0.616 · neurodegeneration · 2026-04-16

## **Molecular Mechanism and Rationale** The nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway represents a

SIRT6-NAD+ Axis Enhancement Therapy

Score: 0.612 · neurodegeneration · 2026-04-02

## Mechanistic Overview SIRT6-NAD+ Axis Enhancement Therapy starts from the claim that modulating SIRT6 within the disea

NAD+/SARM1 Axis Provides Metabolic Feedback Coupling Mitophagy to ER-Phagy

Score: 0.578 · neurodegeneration · 2026-04-21

## **Molecular Mechanism and Rationale** The NAD+/SARM1 axis represents a critical metabolic checkpoint that coordinate

CD38 Inhibition for NAD+ Restoration and Microglial Senescence Prevention

Score: 0.575 · neurodegeneration · 2026-04-25

High risk. The Expert identifies a fatal flaw: CD38 is predominantly expressed in peripheral immune cells (B cells, T ce

NAD+ Precursor Supplementation to Reverse Poly(ADP-ribose) Polymerase-Driven Met

Score: 0.520 · metabolomics · 2026-04-25

NAD+ Precursor Supplementation to Reverse Poly(ADP-ribose) Polymerase-Driven Metabolic Catastrophe

NAD+

Understanding Entity Pages

Wiki Pages (11)

NAD+ Precursors for Neurodegeneration

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

Section 103: Sirtuin Pathway and NAD+-Dependent Deacetylases in CBS/PSP

NAD+ Metabolism in Neurodegeneration

NAD+ Metabolism Pathway in Neurodegeneration

NAD+ Precursors (NMN/NR) for Parkinson's Disease

NAD+ Bioenergetics Investment Synthesis

NAD+ Boosters for Neurodegeneration

NAD+ Precursor Therapy for Neurodegenerative Diseases

CD38 Inhibition + NAD+ Precursor Synergy for Neuroprotection

NAD+ Boosters for Neurodegeneration

Pathway Diagram

Outgoing (9)

Incoming (16)

Targeting Hypotheses (12)

Mentioning Analyses (3)

Microglial subtypes in neurodegeneration — friend vs foe

Investigate mechanisms of epigenetic reprogramming in aging neurons

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

Experiments (7)

Related Papers (20)

Debates (4)

Investigate mechanisms of epigenetic reprogramming in aging neurons [TARGET_ART

Investigate mechanisms of epigenetic reprogramming in aging neurons

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Related Research

SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-Dependent Axon Degene

Mitochondrial NAD+ Salvage Enhancement

NAMPT-Centered NAD+ Restoration to Reverse Basal Forebrain Cholinergic Neuron Me

SIRT6-NAD+ Axis Enhancement Therapy

NAD+/SARM1 Axis Provides Metabolic Feedback Coupling Mitophagy to ER-Phagy

CD38 Inhibition for NAD+ Restoration and Microglial Senescence Prevention

NAD+ Precursor Supplementation to Reverse Poly(ADP-ribose) Polymerase-Driven Met