Official Symbol: TXN
Official Full Name: Thioredoxin
Gene Type: Protein Coding
Location: Chromosome 9q31.3
NCBI Gene ID: 7295
Ensembl ID: ENSG00000136810
UniProt ID: P10599
Thioredoxin (TXN) is a small (12 kDa) ubiquitous antioxidant protein that plays a central role in cellular redox homeostasis. It is a key component of the thioredoxin system, which includes thioredoxin reductase (TXNRD) and NADPH. TXN maintains a reduced intracellular environment by catalyzing disulfide bond reduction in target proteins, thereby protecting cells from oxidative stress. In the nervous system, TXN is essential for neuronal survival, synaptic function, and protection against neurodegenerative processes.
- Active Site: Cys-Gly-Pro-Cys motif mediates redox reactions
- Reducing Power: Uses NADPH via TXNRD to maintain reduced state
- Substrate Range: Reduces peroxiredoxins, ribonucleotide reductase, transcription factors
- ROS Scavenging: Directly neutralizes reactive oxygen species
- Peroxiredoxin Reduction: Recycles peroxiredoxins to active form
- DNA Synthesis: Maintains ribonucleotide reductase in active form
- Disulfide Reduction: Repairs oxidized cysteine residues in proteins
- Chaperone Function: Helps maintain proper protein folding
- Apoptosis Regulation: Interacts with ASK1, NF-κB signaling
- Synaptic Plasticity: Modifies NMDA receptor and AMPAR function
- Neuroprotection: Protects against excitotoxicity and oxidative stress
- Myelin Maintenance: Important for oligodendrocyte function
- Redox Imbalance: TXN system impaired in AD brain
- Therapeutic Target: TXN-boosting compounds in development
- Interaction with Aβ: TXN levels correlate with amyloid pathology
- Oxidative Stress: Central to PD pathogenesis
- Neuroprotection: TXN overexpression protects dopaminergic neurons
- DJ-1 Connection: Synergistic antioxidant system
- SOD1 Mutations: TXN system interacts with mutant SOD1
- Therapeutic Potential: TXN delivery shows promise in models
- Ischemic Injury: TXN reduced after stroke
- Neuroprotection: Exogenous TXN reduces infarct size
- Blood-Brain Barrier: Protects BBB integrity
- Dual Role: Both tumor-promoting and tumor-suppressing functions
- Therapeutic Target: TXNRD inhibitors in cancer therapy
- Neurons: High expression in cortical and hippocampal neurons
- Astrocytes: Expressed in reactive astrocytes
- Oligodendrocytes: Important for myelin maintenance
- Microglia: Upregulated in neuroinflammation
- Transcriptional: Induced by oxidative stress via Nrf2
- Post-translational: Redox-regulated activity
- Cellular Localization: Cytosolic and nuclear isoforms
- TXN Peptides: Cell-penetrating TXN-derived peptides
- TXNRD Inhibitors: Auranofin, arsenic trioxide for cancer
- Nrf2 Activators: Increase endogenous TXN expression
- Neurodegeneration: TXN-based therapies in clinical trials
- Cardiovascular: TXN for ischemic injury
- Aging: TXN decline reversed in models
- Holmgren A et al., Thioredoxin and thioredoxin reductase (2007)
- Masutani H et al., Thioredoxin in brain injury and neuroprotection (2004)
- Lovell MA et al., Thioredoxin in Alzheimer's disease (2000)
- Tobe K et al., Thioredoxin and Parkinson's disease (2003)
- Andersen JK et al., Oxidative stress and neurodegeneration (2004)
- Jiang B et al., Thioredoxin in stroke (2021)
- Sasakura C et al., Thioredoxin and ALS (2010)
- Kaimul AM et al., Thioredoxin in synaptic plasticity (2007)