NAMPT Gene

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gene1368 wordssynced 2026-04-02

NAMPT (Nicotinamide Phosphoribosyltransferase / Visfatin / PBEF)

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NAMPT (Nicotinamide Phosphoribosyltransferase / Visfatin / PBEF)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">NAMPT Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>NAMPT</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Nicotinamide Phosphoribosyltransferase</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>Visfatin, PBEF, PBEF1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7q22.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10135</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>608064</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000105835</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q99714</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein Coding</td>
</tr>
<tr>
<td class="label">Sirtuin</td>
<td>Neuronal Function</td>
</tr>
<tr>
<td class="label">SIRT1</td>
<td>Deacetylates PGC-1alpha, FOXO, tau; promotes mitochondrial biogenesis</td>
</tr>
<tr>
<td class="label">SIRT2</td>
<td>Deacetylates tubulin, alpha-synuclein; regulates oligodendrocyte differentiation</td>
</tr>
<tr>
<td class="label">SIRT3</td>
<td>Deacetylates SOD2, IDH2 in mitochondria; antioxidant protection</td>
</tr>
<tr>
<td class="label">SIRT5</td>
<td>Desuccinylates glutamate dehydrogenase; metabolic regulation</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Cortical neurons</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampal neurons</td>
<td>High</td>
</tr>
<tr>
<td class="label">Astrocytes</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Moderate-High</td>
</tr>
<tr>
<td class="label">Dopaminergic neurons</td>
<td>High</td>
</tr>
<tr>
<td class="label">Motor neurons</td>
<td>High</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">SIRT1</td>
<td>Transcriptional regulation of NAMPT</td>
</tr>
<tr>
<td class="label">FOXO3</td>
<td>NAMPT transcription activation</td>
</tr>
<tr>
<td class="label">PARP1</td>
<td>NAD+ competition</td>
</tr>
<tr>
<td class="label">NMNAT1-3</td>
<td>Downstream enzyme</td>
</tr>
<tr>
<td class="label">PGC-1alpha</td>
<td>SIRT1 substrate (NAD+-dependent)</td>
</tr>
<tr>
<td class="label">Model</td>
<td>NAMPT Manipulation</td>
</tr>
<tr>
<td class="label">NAMPT neuron knockout</td>
<td>Neuronal-specific Nampt deletion</td>
</tr>
<tr>
<td class="label">NAMPT overexpression</td>
<td>Neuronal Nampt overexpression</td>
</tr>
<tr>
<td class="label">NMN supplementation</td>
<td>Dietary NMN</td>
</tr>
<tr>
<td class="label">Visual cortex degeneration</td>
<td>NAMPT inhibition</td>
</tr>
<tr>
<td class="label">Retinal ganglion cells</td>
<td>NAMPT knockdown</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">NMN</td>
<td>NAD+ precursor</td>
</tr>
<tr>
<td class="label">NR (Niagen)</td>
<td>NAD+ precursor</td>
</tr>
<tr>
<td class="label">P7C3 derivatives</td>
<td>NAMPT activator</td>
</tr>
<tr>
<td class="label">SRT2104</td>
<td>SIRT1 activator</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/atopic-dermatitis" style="color:#ef9a9a">Atopic Dermatitis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">284 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Overview

NAMPT (Nicotinamide Phosphoribosyltransferase), also known as visfatin or pre-B cell colony-enhancing factor (PBEF), encodes the rate-limiting enzyme in the [NAD+ salvage pathway](/mechanisms/nad-metabolism-neurodegeneration)[@houtkooper2010]. NAMPT catalyzes the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN), which is then converted to NAD+ by NMN adenylyltransferases (NMNATs)[@pmid28877980][@pmid38580317].

NAD+ is an essential cofactor for metabolic enzymes including sirtuins (SIRT1-7), poly(ADP-ribose) polymerases (PARPs), CD38/CD157, and NAD+dependent dehydrogenases. Declining NAD+ levels with age are a hallmark of metabolic dysfunction and neurodegeneration[@revard2019]. NAMPT is therefore a critical node linking cellular energetics, protein acetylation status, and neuronal survival in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis) (ALS)[@rhyu2018].

Gene Information

Protein Structure and Biochemistry

NAMPT is a homodimeric enzyme (~52 kDa per subunit) that catalyzes the first and rate-limiting step of NAD+ salvage[@rhyu2018]:

Nicotinamide + PRPP (5-phosphoribosyl-1-pyrophosphate) → NMN + PPi

This reaction requires:

Substrates: Nicotinamide (vitamin B3), PRPP
Co-factors: Mg^2+ ions
Energetics: One PRPP bond consumed per NMN produced

The enzyme has two conformations: an open state for substrate binding and a closed state during catalysis. NAMPT activity is regulated by:

Transcriptional control: SIRT1 deacetylates FOXO factors that regulate NAMPT expression
Protein-protein interactions: PARP1 activation depletes NAD+, triggering compensatory NAMPT upregulation
Post-translational modification: NAMPT is phosphorylated at S195, affecting its enzymatic activity

Biological Functions

NAD+ Salvage Pathway

NAMPT is the gatekeeper of the NAD+ salvage pathway[@houtkooper2010]:

Nicotinamide ingestion: Dietary niacin (vitamin B3) and endogenous nicotinamide provide the substrate

NAMPT reaction: Converts nicotinamide to NMN — the rate-limiting step

NMNAT reaction: NMN is converted to NAD+ by NMN adenylyltransferases (NMNAT1-3)

NAD+ consumption: Used by sirtuins, PARPs, CD38, and other NAD+-dependent enzymes

The salvage pathway is the predominant NAD+ source in most tissues. In the brain, the de novo pathway from tryptophan is minimal, making NAMPT-dependent salvage critical for neuronal NAD+ maintenance[@harney2016].

Sirtuin Regulation

NAD+ is the essential cofactor for sirtuin deacetylases[@rhyu2018]:

Sirtuin activity is directly proportional to NAD+/NAM ratio. When NAMPT is low or NAD+ is consumed rapidly by PARPs, sirtuin function declines.

PARP and CD38 Activity

NAD+ is consumed by[@houtkooper2010]:

PARP1/2: DNA repair; activated by oxidative damage (highly elevated in neurodegeneration)
PARP2: Also involved in energy metabolism
CD38/CD157: Cyclic ADP-ribose production; calcium signaling; declines with age

These enzymes can deplete neuronal NAD+ to <50% of baseline during stress, creating a metabolic crisis that NAMPT helps buffer.

Role in Neurodegenerative Diseases

Alzheimer's Disease

NAMPT and NAD+ metabolism are dysregulated in AD[@rhyu2018]:

NAD+ decline: NAD+ levels decrease ~30-50% in AD brain, correlating with cognitive decline
NAMPT downregulation: NAMPT expression is reduced in AD hippocampus and cortex
SIRT1 impairment: Reduced SIRT1 activity leads to P-tau accumulation, mitochondrial dysfunction, and impaired autophagy
Therapeutic potential: NMN and NR supplementation improve AD phenotypes in mouse models

Key studies in AD-NAMPT research[@rhyu2018]:

NMN supplementation improves cognitive function in 3xTg-AD mice
NAMPT overexpression protects against amyloid-beta toxicity in cell models
SIRT1 activation reduces A-beta production through ADAM10 activation

Parkinson's Disease

In PD, NAMPT supports dopaminergic neuron survival[@rhyu2018]:

NAD+ preservation: NAMPT activity protects against 6-OHDA and MPTP toxicity in models
Mitochondrial function: SIRT3 activity (NAD+-dependent) maintains mitochondrial homeostasis in [substantia nigra](/brain-regions/substantia-nigra) neurons
Alpha-synuclein interaction: NAD+ depletion exacerbates synuclein aggregation; restoration is protective
PARP overactivation: Oxidative stress in PD activates PARPs, consuming NAD+ and creating a vicious cycle

NMN supplementation improves mitochondrial function and motor performance in MPTP-induced PD models.

ALS (Amyotrophic Lateral Sclerosis)

NAD+ dysregulation in ALS[@rhyu2018]:

NAD+ depletion: Motor neurons show reduced NAD+ and NAMPT in ALS models
SIRT1 dysfunction: Reduced SIRT1 activity correlates with disease progression
Axonal NAD+ transport: NMN may be transported along axons to support distal compartments
NMNAT compensation: NMNAT3 overexpression is neuroprotective in SOD1G93A mice

Therapeutic strategies targeting NAD+ biosynthesis show promise in preclinical ALS models.

Expression Pattern

NAMPT is expressed in:

Brain NAMPT expression follows circadian oscillations (~24h cycle) driven by the molecular clock. Disruption of circadian rhythm (common in neurodegeneration) impairs NAD+ homeostasis.

Therapeutic Strategies

NAD+ Precursors

Direct supplementation bypasses the NAMPT bottleneck[@rhyu2018]:

NMN (Nicotinamide Mononucleotide): Directly converted to NAD+; crosses some membrane barriers; doses 100-500 mg/day in clinical trials
NR (Nicotinamide Riboside): Converted to NMN intracellularly; FDA-designated GRAS; well-tolerated in humans
Nicotinamide (NAM): Direct NAMPT substrate; high doses may inhibit sirtuins (product feedback)

NAMPT Activators

Small molecules that enhance NAMPT catalytic activity:

P7C3 series: NAMPT activators that promote neurogenesis and protect neurons; P7C3-A20 entered preclinical development
NATs (NAMPT activity enhancers): Several compounds in discovery phase targeting the enzyme's allosteric sites

NAMPT Inhibitors (for cancer, not neurodegeneration)

FK866 (Daporinad): Potent NAMPT inhibitor used in oncology; neurotoxic at high doses
CHS-828 (GMI-1271): NAMPT inhibitor in cancer trials

Sirtuin Activation

Indirect NAMPT pathway targeting:

SRT2104: SIRT1 activator; improves metabolic parameters
SRT1720: SIRT1 activator; extends lifespan in mice

Interaction Partners and Pathways

Key Signaling Pathways

NAMPT → NAD+ → SIRT1 → FOXO/PGC-1alpha: Stress resistance and mitochondrial function

PARP activation → NAD+ depletion → NAMPT upregulation: Compensatory response

Circadian clock → BMAL1/CLOCK → NAMPT: Rhythmic NAD+ oscillation

Animal Models

Clinical Development

No NAMPT-targeted therapies are approved specifically for neurodegeneration, but multiple NAD+ precursor trials are ongoing for age-related cognitive decline.

Biomarkers

Plasma NAMPT: Can be measured by ELISA; correlates with metabolic health
NAD+ levels: Direct measurement in peripheral blood mononuclear cells (PBMCs)
eNAMPT (extracellular): Circulating NAMPT from adipose tissue; cytokine-like activity

External Links

[NCBI Gene - NAMPT](https://www.ncbi.nlm.nih.gov/gene/10135)
[UniProt - Q99714](https://www.uniprot.org/uniprot/Q99714)
[OMIM - 608064](https://www.omim.org/entry/608064)
[GeneCards - NAMPT](https://www.genecards.org/cgi-bin/carddisp.pl?gene=NAMPT)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Senescence-Activated NAD+ Depletion Rescue](/hypothesis/h-cb833ed8) — <span style="color:#81c784;font-weight:600">0.62</span> · Target: CD38/NAMPT

Pathway Diagram

The following diagram shows the key molecular relationships involving NAMPT Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

NAMPT Gene

NAMPT (Nicotinamide Phosphoribosyltransferase / Visfatin / PBEF)

NAMPT (Nicotinamide Phosphoribosyltransferase / Visfatin / PBEF)

Pathway Diagram

Overview

Gene Information

Protein Structure and Biochemistry

Biological Functions

NAD+ Salvage Pathway

Sirtuin Regulation

PARP and CD38 Activity

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

ALS (Amyotrophic Lateral Sclerosis)

Expression Pattern

Therapeutic Strategies

NAD+ Precursors

NAMPT Activators

NAMPT Inhibitors (for cancer, not neurodegeneration)

Sirtuin Activation

Interaction Partners and Pathways

Key Signaling Pathways

Animal Models

Clinical Development

Biomarkers

See Also

External Links

Related Hypotheses

Pathway Diagram