| GLO1 Protein | |
|---|---|
| Protein Name | Glyoxalase 1 |
| Gene Symbol | [GLO1](/genes/glo1) |
| UniProt ID | [Q04760](https://www.uniprot.org/uniprot/Q04760) |
| PDB Structures | 1GLO, 1BH5, 2E0E |
| Molecular Weight | 20,977 Da |
| Subcellular Localization | Cytoplasm |
| Protein Family | Glyoxalase family |
GLO1 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Glyoxalase 1 (GLO1) is a homodimeric metalloenzyme, with each subunit containing a binding site for the catalytic cofactor glutathione (GSH). The active enzyme is a homodimer of approximately 42 kDa. Each subunit consists of 184 amino acids and adopts a beta-alpha-beta fold characteristic of the glyoxalase family. The active site contains two zinc ions (Zn2+) that are essential for catalytic activity. The enzyme requires reduced glutathione (GSH) as a cofactor and catalyzes the conversion of methylglyoxal (MGO) and other reactive carbonyl compounds (RCCs) to S-lactoylglutathione.
GLO1 plays a crucial role in cellular defense against carbonyl stress:
In neurons, GLO1 activity is particularly important given the high metabolic rate and glucose utilization of the brain.
GLO1 is significantly downregulated in AD brain, contributing to pathogenesis:
Therapeutic strategies aiming to enhance GLO1 activity show promise in AD models, reducing amyloid pathology and improving cognitive function.
GLO1 dysfunction contributes to PD through:
In ALS:
GLO1 is directly relevant to diabetic complications:
GLO1-based therapeutic strategies include:
GLO1 inhibitors (for cancer):
GLO1 activators (for neurodegeneration):
Combination therapy:
Gene therapy: AAV-mediated GLO1 delivery