| PRDX4 — Peroxiredoxin 4 | |
|---|---|
| Symbol | PRDX4 |
| Full Name | Peroxiredoxin 4 |
| Chromosome | 19p13.13 |
| NCBI Gene | 10599 |
| Ensembl | ENSG00000179673 |
| OMIM | 607723 |
| UniProt | Q9BZL1 |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Amyotrophic Lateral Sclerosis |
| Expression | Cerebral [cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus), Liver, Kidney |
PRDX4 (Peroxiredoxin 4) is a member of the peroxiredoxin family of antioxidant enzymes that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, and peroxynitrite[1]. Unlike cytosolic peroxiredoxins, PRDX4 is localized primarily to the endoplasmic reticulum (ER) and is secreted via the conventional secretory pathway[2]. This unique subcellular localization positions PRDX4 as a critical regulator of ER redox homeostasis and extracellular oxidative stress.
PRDX4 functions as a thiol-dependent peroxidase using a conserved cysteine residue (Cys^157) at its active site to reduce peroxides[3]. The enzyme exhibits the following key functions:
PRDX4 is significantly downregulated in AD brains, particularly in the hippocampus and cerebral cortex[5]. Loss of PRDX4 leads to increased oxidative stress, protein oxidation, and acceleration of amyloid-β pathology. Studies show that PRDX4 overexpression protects against Aβ-induced neurotoxicity in cellular models[6].
In PD models, PRDX4 protects dopaminergic neurons from oxidative stress-induced cell death[7]. The enzyme is implicated in maintaining mitochondrial function and preventing mitochondrial permeability transition.
PRDX4 expression is altered in ALS and may play a protective role against oxidative damage in motor neurons[8].
PRDX4 shows high expression in:
Rhee SG, et al. Peroxiredoxins: A historical overview and novel perspectives. Free Radic Biol Med. 2020. ↩︎
Tavender TJ, et al. Peroxiredoxin 4 is involved in the secretory pathway. J Cell Sci. 2008. ↩︎
Park JW, et al. Crystal structure of human peroxiredoxin 4 at 1.45 Å resolution. J Mol Biol. 2000. ↩︎
Jin DY, et al. Regulation of NF-kappaB by peroxiredoxins. Mol Cells. 2013. ↩︎
Kim SH, et al. Alterations of peroxiredoxin expression in Alzheimer's disease brain. J Neural Transm. 2009. ↩︎
Luo CF, et al. Peroxiredoxin 4 protects against amyloid beta toxicity in Alzheimer's disease. J Alzheimers Dis. 2016. ↩︎
Zhang B, et al. Peroxiredoxin 4 is a novel therapeutic target for Parkinson's disease. Redox Biol. 2020. ↩︎
Arai M, et al. Alteration of peroxiredoxin expression in sporadic amyotrophic lateral sclerosis. Neuropathology. 2010. ↩︎