FASN Gene

FASN Gene

Pathway Diagram

```mermaid
flowchart TD
FAS_gene["FAS<br/>Gene"]
FAS_protein["FAS<br/>Protein"]
FOXO["FOXO<br/>Transcription Factor"]
AMBRA1["AMBRA1<br/>Autophagy Regulator"]

apoptosis["Apoptosis<br/>Cell Death"]
neurodegeneration["Neurodegeneration<br/>Disease Process"]
neuroinflammation["Neuroinflammation<br/>Immune Response"]

alzheimer["Alzheimer's<br/>Disease"]
als["ALS<br/>Disease"]
ms["Multiple<br/>Sclerosis"]

TNF["TNF<br/>Cytokine"]
IL6["IL6<br/>Cytokine"]
APOE["APOE<br/>Lipid Transport"]

inflammation["Chronic<br/>Inflammation"]
aging["Cellular<br/>Aging"]
senescence["Cellular<br/>Senescence"]

FOXO -->|"activates"| FAS_gene
AMBRA1 -->|"regulates"| FAS_protein
FAS_gene -->|"encodes"| FAS_protein

FAS_protein -->|"activates"| apoptosis
FAS_gene -->|"activates"| neurodegeneration
FAS_gene -->|"activates"| neuroinflammation

FAS_gene -->|"activates"| alzheimer
FAS_gene -->|"activates"| als
FAS_gene -->|"activates"| ms

FAS_gene -->|"activates"| TNF
FAS_gene -->|"activates"| IL6
FAS_gene -->|"interacts_with"| APOE

FAS_gene -->|"regulates"| inflammation
FAS_gene -->|"regulates"| aging
FAS_gene -->|"regulates"| senescence

apoptosis -->|"contributes_to"| neurodegeneration
neuroinflammation -->|"promotes"| neurodegeneration

style FAS_gene fill:#006494
style FAS_protein fill:#006494
style AMBRA1 fill:#4a1a6b
style FOXO fill:#4a1a6b
style apoptosis fill:#ef5350

FASN Gene

Pathway Diagram

Introduction

Fasn Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<nav class="infobox .infobox-gene"> [@pihlajamaki2009]
| FASN Gene | | [@rohrig2015]
|---|---| [@suagee2013]
| Full Name | Fatty Acid Synthase | [@wang2020]
| Symbol | FASN | [@menendez2007]
| Chromosome | 1q25 | [@kuhajda2008]
| NCBI Gene ID | 2194 | [@zhang2017]
| OMIM | 600005 | [@liu2021]
| Ensembl ID | ENSG00000169710 | [@van2023]
| UniProt | P49327 |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Metabolic Disorders, Cancer |
</nav>

Overview

The FASN gene encodes fatty acid synthase (FASN), a crucial metabolic enzyme that catalyzes the de novo synthesis of long-chain fatty acids. Located on chromosome 1q25, FASN is one of the largest enzyme complexes in cellular metabolism, functioning as a type I fatty acid synthase that performs all catalytic steps in fatty acid synthesis within a single polypeptide [1].

FASN is particularly significant in the context of neurodegenerative diseases because brain lipid metabolism is essential for neuronal function, membrane maintenance, and myelin synthesis. Dysregulation of FASN has been implicated in Alzheimer's disease, Parkinson's disease, and various metabolic disorders affecting the central nervous system [2].

Gene Structure and Function

Catalytic Domains

The FASN protein contains multiple functional domains arranged in a linear array:

Biochemical Function

FASN catalyzes the synthesis of palmitate (C16:0) as its primary product from simpler precursors:

• Primary substrate: Acetyl-CoA (primer) and malonyl-CoA ( extender)
• Cofactors required: NADPH (reducing power)
• Final product: Palmitate (16-carbon saturated fatty acid)
• Reaction stoichiometry: 8 acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+ → palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O

Normal Function in the Brain

Lipid Metabolism

In the central nervous system, FASN plays several important roles [3]:

• De novo lipogenesis: Synthesis of fatty acids for membrane phospholipids
• Myelin maintenance: Supplying lipids for myelin sheath integrity
• Synaptic vesicle formation: Providing lipids for neurotransmitter release
• Lipid droplet formation: Energy storage in neurons and glia

Cellular Localization

FASN expression in the brain:

• [Neurons](/entities/neurons): Moderate expression, higher in metabolically active neurons
• [Astrocytes](/entities/astrocytes): High expression, involved in lipid provision to neurons
• Oligodendrocytes: Essential for myelin lipid synthesis
• [Microglia](/entities/microglia): Modulated expression during immune activation

Disease Associations

Alzheimer's Disease [2][4]

FASN dysregulation is increasingly recognized in AD pathophysiology:

• Upregulation in AD brain: FASN expression is elevated in AD hippocampus and [cortex](/brain-regions/cortex)
• Amyloid interaction: FASN activity may influence [APP](/entities/app-protein) processing and [Aβ](/proteins/amyloid-beta) generation
• Lipid homeostasis disruption: Altered fatty acid metabolism contributes to membrane abnormalities
• Mitochondrial dysfunction: FASN-derived lipids affect mitochondrial function
• Neuroinflammation: Lipid mediators from FASN modulate glial activation

| FASN Alteration | Consequence in AD |
|-----------------|-------------------|
| Increased expression | Altered membrane lipid composition |
| Enhanced activity | Elevated ceramide levels |
| Dysregulated localization | Impaired synaptic function |
| Interaction with [BACE1](/entities/bace1) | Potential influence on amyloidogenesis |

Parkinson's Disease [5]

FASN involvement in PD includes:

• Mitochondrial lipid metabolism: FASN provides lipids for mitochondrial membranes
• [α-synuclein](/proteins/alpha-synuclein) interaction: Lipid environments affect α-synuclein aggregation
• Dopaminergic neuron vulnerability: Lipid homeostasis critical for neuronal survival
• L-DOPA metabolism: Fatty acids influence dopaminergic signaling

Metabolic Disorders

FASN is central to metabolic disease pathogenesis:

• Obesity: Elevated hepatic FASN activity
• Insulin resistance: FASN dysregulation in metabolic syndrome
• Type 2 diabetes: Connection to insulin signaling pathways
• Fatty liver disease: Hepatic FASN overexpression

Cancer

FASN is overexpressed in numerous cancers [6]:

• Breast cancer: FASN is a prognostic marker
• Prostate cancer: Androgen regulates FASN expression
• Ovarian cancer: Associated with aggressive disease
• Therapeutic target: FASN inhibitors in clinical trials

Expression Pattern

Brain Region Distribution

FASN shows region-specific expression:

• [Hippocampus](/brain-regions/hippocampus): High expression in CA regions and dentate gyrus
• Cerebral cortex: Layer-specific patterns
• Cerebellum: Moderate expression in Purkinje cells
• Substantia nigra: Important for dopaminergic neuron function
• White matter: Lower expression, myelin regions

Developmental Regulation

• Fetal brain: High expression during development
• Adult brain: Maintained at moderate levels
• Aging: Altered expression patterns
• Disease states: Frequently upregulated

Regulation Mechanisms

FASN expression is regulated by:

Therapeutic Targeting

FASN Inhibitors

Several FASN inhibitors have been developed [7]:

| Compound | Stage | Specificity |
|----------|-------|-------------|
| Orlistat | Clinical use | Irreversible inhibitor |
| C75 | Preclinical | Synthetic inhibitor |
| GSK2194069 | Preclinical | Selective FASN inhibitor |
| IPI-9119 | Preclinical | FASN-specific |

neurodegenerative Disease Applications

• AD therapeutic potential: Modulating FASN to restore lipid homeostasis
• PD applications: Protecting dopaminergic neurons through lipid management
• Combination therapies: FASN inhibitors with other metabolic modulators

Key Publications

Background

The study of Fasn Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Lipid Metabolism Pathway](/mechanisms/lipid-metabolism-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• Metabolic Syndromes
• SREBP1 Gene
• SCD1 Gene
• ABCA1 Gene

External Links

• [NCBI Gene: FASN](https://www.ncbi.nlm.nih.gov/gene/2194)
• [UniProt: P49327](https://www.uniprot.org/uniprot/P49327)
• [OMIM: 600005](https://www.omim.org/entry/600005)
• [Ensembl: ENSG00000169710](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000169710)

References

Pathway Diagram

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