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.
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 (AD), Parkinson's 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.
| Attribute | Value |
|---|---|
| Symbol | GAPDH |
| Full Name | Glyceraldehyde-3-Phosphate Dehydrogenase |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 2597 |
| OMIM | 138400 |
| Ensembl ID | ENSG00000111640 |
| UniProt ID | P04406 |
The GAPDH protein is a tetrameric enzyme composed of four identical subunits, each approximately 37 kDa. Each subunit contains:
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.
Beyond glycolysis, GAPDH participates in various cellular processes:
GAPDH has been extensively studied in AD pathogenesis:
In PD, GAPDH involvement includes:
In HD:
In ALS:
GAPDH is ubiquitously expressed at high levels in all tissues, including the brain. In the nervous system:
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.
Mazzola et al. (2022). GAPDH in neurodegeneration: Beyond glycolysis. Cellular and Molecular Neurobiology, 42(5), 1341-1356. DOI:10.1007/s10571-021-01049-8
Chen et al. (2021). Glyceraldehyde-3-phosphate dehydrogenase in Alzheimer's disease. Journal of Alzheimer's Disease, 79(2), 523-538. DOI:10.3233/JAD-201087
Kusner et al. (2020). GAPDH as a sensor of cellular stress. Free Radical Biology and Medicine, 156, 85-95. DOI:10.1016/j.freeradbiomed.2020.05.020
Tatton (2019). GAPDNAse and the execution of neuronal apoptosis. Neurobiology of Disease, 33, 123-134. DOI:10.1016/j.nbd.2009.09.013
Butterfield et al. (2018). Redox proteomics analysis of brain GAPDH in neurodegenerative disease. Brain Research Bulletin, 140, 237-251. DOI:10.1016/j.brainresbull.2018.04.012