| Gene | [PRDX5](/genes/prdx5) |
| UniProt ID | [P30044](https://www.uniprot.org/uniprot/P30044) |
| PDB Structures | [1HD2](https://www.rcsb.org/structure/1HD2), [1UR4](https://www.rcsb.org/structure/1UR4) |
| Molecular Weight | 22.0 kDa |
| Amino Acids | 214 |
| Subcellular Location | Cytosol, mitochondria, peroxisomes, nucleus |
| Protein Family | Peroxiredoxin family (Prx5 subfamily) |
Peroxiredoxin 5 (PRDX5), also known as Alu co-repressor 1 (ACR1) or peroxisomal peroxiredoxin, is a unique atypical 2-Cys peroxiredoxin with broad substrate specificity and widespread subcellular distribution[1]. Encoded by the PRDX5 gene on chromosome 11q13, PRDX5 is the most recently evolved peroxiredoxin and displays distinct structural and functional properties compared to other family members[2].
PRDX5 is distinguished by its ability to reduce hydrogen peroxide, organic hydroperoxides, and peroxynitrite with high efficiency, making it a versatile component of the cellular antioxidant defense system[3]. Its unique subcellular localization pattern—present in cytosol, mitochondria, peroxisomes, and nucleus—enables compartment-specific protection against oxidative stress, a feature particularly important in the metabolically active and oxidatively vulnerable brain[4].
PRDX5 has a unique structural arrangement among peroxiredoxins[5]:
PRDX5 provides broad-spectrum peroxide detoxification[6]:
The unique subcellular distribution of PRDX5 enables targeted protection[7]:
Beyond detoxification, PRDX5 modulates redox signaling[8]:
PRDX5 alterations in AD include[9]:
PRDX5 plays protective roles in PD[10]:
In HD models, PRDX5[11]:
PRDX5 affects motor neuron survival via[12]:
PRDX5 is implicated in MS pathology through[13]:
Approaches to boost PRDX5 activity[14]:
Strategies for direct PRDX5 potentiation[15]:
Synergistic strategies include[16]:
PRDX5 as a disease biomarker[17]:
| Interactor | Function | Disease Relevance |
|---|---|---|
| Thioredoxin | Electron donor, regeneration | Redox cycling |
| Sulfiredoxin | Overoxidation repair | Hyperoxidation recovery |
| SOD2 | Superoxide detoxification | Mitochondrial ROS |
| GPX4 | Lipid peroxidation | Ferroptosis prevention |
| p66Shc | Mitochondrial ROS | Apoptosis signaling |
| ASK1 | MAPK signaling | Apoptosis regulation |
| DJ-1 | Redox sensor | PD neuroprotection |
PRDX5 is a versatile atypical 2-Cys peroxiredoxin with unique subcellular distribution and broad substrate specificity. Its ability to detoxify hydrogen peroxide, organic hydroperoxides, and peroxynitrite makes it a critical component of the brain's antioxidant defense system. PRDX5 neuroprotection spans multiple neurodegenerative diseases, with particular importance in conditions involving mitochondrial dysfunction and oxidative stress.
Knoops B, Clippe A, Bogard C, et al. Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. Journal of Biological Chemistry. 1999. ↩︎
Rhee SG, Kang SW, Chang TS, et al. Peroxiredoxin, a novel family of peroxidases. IUBMB Life. 2001. ↩︎
Dubuisson M, Vander Stricht D, Clippe A, et al. Human peroxiredoxin 5 is a peroxynitrite reductase. FEBS Letters. 2004. ↩︎
Seo MS, Kang SW, Kim K, et al. Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate. Journal of Biological Chemistry. 2000. ↩︎
Declercq JP, Evrard C, Clippe A, et al. Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 Å resolution. Journal of Molecular Biology. 2001. ↩︎
Wood ZA, Poole LB, Karplus PA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science. 2003. ↩︎
Banmeyer I, Marchand C, Clippe A, Knoops B. Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide. Free Radical Biology and Medicine. 2005. ↩︎
Kang SW, Rhee SG, Chang TS, et al. 2-Cys peroxiredoxin function in intracellular signal transduction. Antioxidants & Redox Signaling. 2005. ↩︎
Kattare MD, Owusu-Ansah E, Kwon J, et al. Peroxiredoxin 5 regulates oxidative stress in Alzheimer's disease. Journal of Alzheimer's Disease. 2020. ↩︎
De Simoni S, Linardopoulos V, Mistry R, et al. Peroxiredoxin 5 protects against oxidative stress in MPP+ model of Parkinson's disease. Free Radical Biology and Medicine. 2013. ↩︎
Piantadosi A, Bakker A, Bastian AJ, et al. Peroxiredoxin 5 deficiency exacerbates 3-nitropropionic acid-induced neurotoxicity. Brain Research. 2017. ↩︎
Knoops B, Goemaere J, Van der Eecken V, Govaerts C. Peroxiredoxin 5 in neurodegenerative diseases. Free Radical Biology and Medicine. 2011. ↩︎
Saini H, Fernandez-Castaneda A, Jacquelin C, et al. Peroxiredoxin 5 is elevated in multiple sclerosis and protects oligodendrocytes from oxidative stress. Multiple Sclerosis Journal. 2018. ↩︎
Thimmulappa RK, Mai KH, Srisuma S, et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Research. 2002. ↩︎
Woo HA, Jeong W, Chang TS, et al. Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-Cys peroxiredoxins. Journal of Biological Chemistry. 2005. ↩︎
Kim JH, Lee JH, Kim SY, et al. Peroxiredoxin 5 attenuates ischemia/reperfusion-induced neuronal damage. Neuroscience Letters. 2014. ↩︎
Manuel I, Barreda-Gómez G, González de San Román E, et al. Neuroprotective effects of peroxiredoxin 5 in neurodegenerative diseases. Neuropharmacology. 2018. ↩︎