entity

NAD+ depletion

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NAD+ depletion: 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.

79Connections

3Hypotheses

4Analyses

50Outgoing

29Incoming

7Experiments

5Debates

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Outgoing (50)

Target	Relation	Type	Str
alzheimer_disease	biomarker_for	disease	0.95
lipid_droplet_biogenesis	causes	pathway	0.95
neuroinflammation	causes	mechanism	0.95
neuroimmune dysfunction	causes	unknown	0.95
ATF3	activates	unknown	0.95
PARP1 activation	causes	protein	0.95
neuroinflammation	contributes_to	mechanism	0.95
PD-L1	upregulates	unknown	0.95
neuronal_dysfunction	contributes_to	unknown	0.90
microglial_activation	contributes_to	mechanism	0.90
NOX2	upregulates	unknown	0.90
ferroptosis	contributes_to	mechanism	0.90
genomic instability	causes	mechanism	0.90
mitochondrial dysfunction	associated_with	mechanism	0.90
mitochondrial myopathy	biomarker_for	unknown	0.90
SIRT1 activity	inhibits	enzyme_activity	0.90
IDH-mutant tumors	associated_with	unknown	0.90
autophagy	associated_with	pathway	0.90
NAT10	associated_with	unknown	0.90
neuronal senescence	associated_with	unknown	0.85
muscle strength	correlates_with	unknown	0.85
mitochondrial dysfunction	contributes_to	mechanism	0.85
microglial_activation	causes	mechanism	0.85
mitochondrial dysfunction	causes	mechanism	0.85
mitochondrial biogenesis	inhibits	mechanism	0.85
mitochondrial_dysfunction	contributes_to	mechanism	0.85
cellular survival	inhibits	unknown	0.85
Aging	associated_with	disease	0.85
Neurodegeneration	associated_with	disease	0.85
Aging	associated_with	disease	0.85
Metabolic Disorders	associated_with	disease	0.85
oxidative stress	contributes_to	mechanism	0.80
mitochondrial_dysfunction	causes	mechanism	0.80
cognitive impairment	associated_with	unknown	0.80
neuronal dysfunction	causes	phenotype	0.80
Neurodegeneration	associated_with	disease	0.80
circadian disruption	associated_with	mechanism	0.75
mitochondrial_dysfunction	associated_with	mechanism	0.75
microglial_activation	modulates	mechanism	0.75
alzheimers	associated_with	disease	0.75
oxidative stress	associated_with	mechanism	0.75
Transcriptional lock-in	causes	mechanism	0.70
TFEB	modulates	protein	0.70
HDAC3 inhibition	modulates	mechanism	0.70
SIRT3 inactivation	causes	mechanism	0.70
TFEB	activates	protein	0.70
mitochondrial quality control	impairs	mechanism	0.70
alzheimers	implicated_in	disease	0.65
HDAC3 inhibition	associated_with	mechanism	0.65
glymphatic_clearance	modulates	mechanism	0.65

Incoming (29)

Source	Relation	Type	Str
SIRT	causes	unknown	0.95
NAMPT	causes	unknown	0.95
niacin	inhibits	unknown	0.95
oxidative stress	causes	mechanism	0.95
CD38	mediates	protein	0.95
sirtuin activation	causes	unknown	0.95
SIRT1	causes	unknown	0.95
AEP	causes	unknown	0.90
aging	causes	unknown	0.90
C/EBPβ	causes	unknown	0.90
aging	contributes_to	unknown	0.90
nicotinamide riboside	inhibits	drug	0.90
glycolytic overdrive	causes	unknown	0.90
31689415	leads to	paper	0.90
SIRT1	contributes_to	unknown	0.85
neuroinflammation	associated_with	mechanism	0.85
mitochondrial_dysfunction	associated_with	mechanism	0.75
microglial_activation	contributes_to	mechanism	0.75
oxidative stress	contributes_to	mechanism	0.70
mitochondrial dysfunction	causes	process	0.70
CD38	causes	protein	0.70
oxidative stress	correlates_with	mechanism	0.70
TFEB	modulates	protein	0.70
oxidative stress	associated_with	mechanism	0.70
PARP1	causes	enzyme	0.70
HDAC3 inhibition	modulates	mechanism	0.68
NEURODEGENERATIVE DISORDERS	associated_with	gene	0.60
31812486	is associated with	paper	0.60
31812486	contributes to	paper	0.60

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Senescence-Activated NAD+ Depletion Rescue	0.755	neurodegeneration	Senolytic therapy for age-related neurod
SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-D	0.698	neurodegeneration	What is the molecular mechanism by which
CD38 Inhibition to Prevent NAD+ Depletion and Restore Cellul	0.380	metabolomics	Metabolomic signatures of neurodegenerat

Mentioning Analyses (4)

Scientific analyses that reference this entity

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.629

What is the optimal therapeutic window for microglial reprogramming before irrev

neurodegeneration | 2026-04-06 | 7 hypotheses Top: 0.735

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

neurodegeneration | 2026-04-04 | 0 hypotheses

Senolytic therapy for age-related neurodegeneration

neurodegeneration | 2026-04-01 | 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
NAD(+) metabolism, stemness, the immune response, and cancer. [PMID:33384409]	Navas LE, Carnero A	Signal Transduct Target Ther	2021	1
NAD metabolism fuels human and mouse intestinal inflammation. [PMID:28877980]	Gerner RR, Klepsch V, Macheiner S, Arnha	Gut	2018	1
NAD+ and sirtuins in aging and disease. [PMID:24786309]	Imai S, Guarente L	Trends Cell Biol	2014	1
Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affi [PMID:39676006]	["Waldschmidt J", "Rasche L", "Kort\u00f	Clinical lymphoma, myeloma & l	2025	0
Protein Acetylation and NAD+ Homeostasis in Aging Muscle. [PMID:40879949]	Ji LL	Advances in experimental medic	2025	0
CD38 is a key mediator of NAD+ depletion in the brain of ZIKV-infected mice. [PMID:41362627]	Saraiva GN, Sousa BG, Souza NMS, Vitorin	iScience	2025	0
REV-ERBα regulates brain NAD+ levels and tauopathy via an NFIL3-CD38 axis. [PMID:40890338]	Lee J, Kang R, Park S, Saliu IO, Son M,	Nature aging	2025	0
Structure-based cheminformatics and molecular dynamics profiling of potential SI [PMID:40650732]	Al-Samydai A, Al-Mamoori F, Mayyas A, Or	Molecular diversity	2025	0
Dysregulation of Niacin-Derived NAD+ Salvage Pathway Markers (CD38, NAMPT, SIRT1 [PMID:41470091]	Huwaimel B, Alqarni S, Abouzied AS, Algh	Medicina (Kaunas, Lithuania)	2025	0
Computational Prediction of Amino Acid Preferences of Potentially Multispecific [PMID:38345234]	["Cruz H", "Llanes A", "Fern\u00e1ndez P	Journal of visualized experime	2024	0
The frequency of CD38 [PMID:39358361]	["Pisu D", "Johnston L", "Mattila J", "R	Nature communications	2024	0
Differential Diagnosis of Changes in Intraocular Lenses. [PMID:37567234]	["Yildirim T", "Auffarth G", "Henningsen	Klinische Monatsblatter fur Au	2023	0
Synergistic lethality in chronic myeloid leukemia - targeting oxidative phosphor [PMID:38012567]	["H\u00e4selbarth L", "Gamali S", "Saul	BMC cancer	2023	0
Real-Time Interfacial Nanothermometry Using DNA-PAINT Microscopy. [PMID:35789234]	["Nooteboom S", "Wang Y", "Dey S", "Zijl	Small (Weinheim an der Bergstr	2022	0
Theoretical Study of Vinyl-Sulfonate Monomers and Their Effect as the Dopants of [PMID:36234890]	["Rodr\u00edguez-S\u00e1nchez I", "Conej	Molecules (Basel, Switzerland)	2022	0
Teclistamab in Relapsed or Refractory Multiple Myeloma. [PMID:35661166]	["Moreau P", "Garfall A", "van de Donk N	The New England journal of med	2022	0
Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from tw [PMID:33914175]	["Driouk L", "Schmitt R", "Peters A", "H	Molecular and cellular pediatr	2021	0
Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised [PMID:33567890]	["Wienholtz N", "Christensen C", "Zhang	Cephalalgia : an international	2021	0
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. [PMID:33626253]	["Munshi N", "Anderson L", "Shah N", "Ma	The New England journal of med	2021	0

Debates (5)

Multi-agent debates referencing this entity

Multiple hypotheses assumed microglia could be restored to homeostatic states, b

closed · Rounds: 4 · Score: 0.63 · 2026-04-22

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

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

What is the current clinical trial landscape for AD therapeutics, and which mech

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

Is the amyloid concentration in AD clinical trials rational given lecanemab's ap

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

What are the mechanisms underlying senolytic therapy for age-related neurodegene

closed · Rounds: 4 · Score: 0.92 · 2026-04-01

Related Research

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

No additional research found