GAPDH Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GAPDH Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>GAPDH</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Glyceraldehyde-3-Phosphate Dehydrogenase</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>12p13.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2597</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>138400</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000111640</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P04406</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/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">818 edges</a></td>
</tr>
</table>
Pathway Diagram
Mermaid diagram (expand to render)
Gapdh 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.
Overview
GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) is a well-known metabolic enzyme that plays a central role in glycolysis. Despite its primary function in energy metabolism, GAPDH has been extensively studied for its involvement in neurodegenerative diseases, including [Alzheimer's disease](/diseases/alzheimers-disease) (AD), [Parkinson's disease](/diseases/parkinsons-disease) (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The gene is located on chromosome 12p13.31 and encodes a 335-amino acid protein. [@chen2021]
Protein Structure
The GAPDH protein is a tetrameric enzyme composed of four identical subunits, each approximately 37 kDa. Each subunit contains:
- NAD+-binding domain: Binds NAD+ as a cofactor
- Catalytic domain: Contains the active site for glyceraldehyde-3-phosphate oxidation
- C-terminal domain: Involved in subunit interactions and tetramer formation
Normal Function
Glycolysis
GAPDH catalyzes the sixth step of glycolysis, converting glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate (1,3-BPG), while NAD+ is reduced to NADH:
Glyceraldehyde-3-phosphate + NAD+ + Pi → 1,3-Bisphosphoglycerate + NADH + H+
This reaction is essential for cellular energy production through anaerobic and aerobic glycolysis.
Additional Cellular Functions
Beyond glycolysis, GAPDH participates in various cellular processes:
- DNA repair: GAPDH has been implicated in DNA repair mechanisms
- [Apoptosis](/entities/apoptosis): Can translocate to the nucleus during apoptosis
- Iron homeostasis: Regulates iron metabolism through interaction with iron regulatory proteins
- tRNA export: Involved in nuclear export of tRNA
- Transcription regulation: Can bind to DNA and regulate gene expression
Role in Neurodegeneration
Alzheimer's Disease
GAPDH has been extensively studied in AD pathogenesis:
- [Amyloid-beta](/proteins/amyloid-beta) interaction: GAPDH binds to amyloid-beta (Aβ) peptides, potentially influencing Aβ aggregation and toxicity
- Energy metabolism dysfunction: Reduced GAPDH activity in AD brains correlates with cognitive decline
- Glycolytic impairment: Decreased glucose metabolism is an early hallmark of AD, with GAPDH being one of the affected enzymes
- Nitrosylation: S-nitrosylation of GAPDH in AD brains inhibits its glycolytic function
Parkinson's Disease
In PD, GAPDH involvement includes:
- Mitochondrial dysfunction: GAPDH translocation to mitochondria may indicate cellular stress
- [Alpha-synuclein](/proteins/alpha-synuclein) aggregation: GAPDH may interact with alpha-synuclein in Lewy bodies
- Oxidative stress: GAPDH is sensitive to oxidative damage in dopaminergic [neurons](/entities/neurons)
Huntington's Disease
In HD:
- Transcriptional dysregulation: GAPDH interacts with mutant [huntingtin protein](/proteins/huntingtin)
- Energy deficit: Reduced GAPDH activity contributes to metabolic dysfunction in HD
- Apoptosis: GAPDH nuclear translocation triggers cell death pathways
Amyotrophic Lateral Sclerosis
In ALS:
- Motor neuron vulnerability: GAPDH aggregates are found in ALS motor neurons
- Oxidative stress: Motor neurons show increased GAPDH oxidation
- Energy metabolism: Altered glycolysis in ALS spinal cord
Expression Pattern
GAPDH is ubiquitously expressed at high levels in all tissues, including the brain. In the nervous system:
- Neurons: High expression in pyramidal neurons of the [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
- [Astrocytes](/entities/astrocytes): Moderate expression
- Oligodendrocytes: Present but lower levels
- [Microglia](/cell-types/microglia-neuroinflammation): Low baseline expression, increased in neuroinflammation
Therapeutic Implications
Biomarker Potential
- GAPDH is commonly used as a loading control in Western blots due to its stable expression
- CSF levels of GAPDH have been investigated as a biomarker for neurodegenerative diseases
- Blood GAPDH activity may reflect systemic metabolic dysfunction
Drug Targets
- GAPDH modulators are being explored for neuroprotection
- Antioxidants may protect GAPDH from oxidative inactivation
- Compounds that enhance GAPDH glycolytic activity are of interest
Background
The study of Gapdh 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.
Brain Atlas Resources
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
- [Allen Human Brain Atlas - GAPDH Expression](https://human.brain-map.org/microarray/search/show?search_term=GAPDH): Gene expression data
See Also
- [Genes](/genes/)
- [Proteins](/proteins/)
- [Alzheimer's Disease](/diseases/alzheimers-disease/)
- [Parkinson's Disease](/diseases/parkinsons-disease/)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction/)
- [Metabolic Pathways](/mechanisms/energy-metabolism/)
External Links
- [NCBI Gene: GAPDH](https://www.ncbi.nlm.nih.gov/gene/2597)
- [UniProt: P04406](https://www.uniprot.org/uniprot/P04406)
- [OMIM: 138400](https://www.omim.org/entry/138400)
- [Ensembl: ENSG00000111640](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000111640)
References
[Mazzola et al, (2022) (2022)](https://doi.org/10.1007/s10571-021-01049-8)
[Chen et al, (2021) (2021)](https://doi.org/10.3233/JAD-201087)
[Kusner et al, (2020) (2020)](https://doi.org/10.1016/j.freeradbiomed.2020.05.020)
[Unknown, Tatton (2019). GAPDNAse and the execution of neuronal apoptosis (2019)](https://doi.org/10.1016/j.nbd.2009.09.013)
[Butterfield et al, (2018) (2018)](https://doi.org/10.1016/j.brainresbull.2018.04.012)Pathway Diagram
The following diagram shows the key molecular relationships involving GAPDH Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)