SRXN1 is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
| Gene | [SRXN1](/genes/srxn1) |
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| UniProt ID | [Q9YGG8](https://www.uniprot.org/uniprot/Q9YGG8) |
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| PDB Structures | 2RKN, 3CBX, 5O8T |
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| Molecular Weight | 14,956 Da |
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| Subcellular Localization | Cytoplasm, Nucleus |
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| Protein Family | Sulfiredoxin family |
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SRXN1 (Sulfiredoxin 1) is a small antioxidant enzyme (125 amino acids) specialized in reducing overoxidized peroxiredoxins (Prxs). It catalyzes the ATP-dependent reduction of cysteine-sulfinic acid back to thiol.
The protein contains:
- N-terminal catalytic domain with conserved cysteine
- C-terminal region for peroxiredoxin interaction
- Forms homodimers
- Requires ATP and magnesium for activity
SRXN1 plays a critical role in antioxidant defense:
- Peroxiredoxin Regeneration: Reduces hyperoxidized Prx-SO2 to Prx-SH, restoring antioxidant activity
- Redox Homeostasis: Maintains cellular redox balance
- H2O2 Signaling: Modulates H2O2-mediated signal transduction
- Stress Response: Induced by oxidative stress via Nrf2
- Protein Thiol Protection: Prevents irreversible oxidation of protein cysteines
SRXN1 is crucial for neuronal survival under oxidative stress:
- SRXN1 expression decreased in AD brains
- Peroxiredoxin hyperoxidation accumulates in AD
- Nrf2-SRXN1 pathway impaired
- Therapeutic: SRXN1 overexpression reduces AD pathology
- SRXN1 protects dopaminergic neurons from oxidative stress
- 6-OHDA and MPTP induce SRXN1
- Deficient SRXN1 increases vulnerability
¶ Stroke and Brain Ischemia
- Ischemia-reperfusion generates massive ROS
- SRXN1 is neuroprotective in stroke models
- Therapeutic window for SRXN1 activation
- Motor neurons vulnerable to oxidative stress
- SRXN1 expression changes in ALS
- Peroxiredoxin system impaired in ALS
- SRXN1 activity declines with age
- Contributes to age-related oxidative stress
- Links aging and neurodegeneration
SRXN1-based therapeutic approaches:
- Gene Therapy: AAV-SRXN1 for neuroprotection
- Nrf2 Activators: Increase SRXN1 expression (sulforaphane, bardoxolone)
- Small Molecule Mimetics: Sulfiredoxin mimetics in development
- Protein Therapy: Recombinant SRXN1
¶ Drug Candidates
- Sulforaphane: Nrf2 activator, increases SRXN1
- Bardoxolone-methyl (CDDO-Me): Nrf2 activator
- Dimethyl fumarate (Tecfidera): Nrf2 activator, approved for MS
- Rhee et al., Peroxiredoxin function and the role of sulfiredoxin (2005)
- Soriano et al., Sulfiredoxin in oxidative stress (2008)
- Lee et al., SRXN1 in Parkinson's disease (2013)
- Kang et al., Nrf2 and antioxidant genes in neurodegeneration (2015)
- Jang et al., Sulfiredoxin and peroxiredoxin in aging (2016)