Official Symbol: GSR
Official Full Name: Glutathione Reductase
Gene Type: Protein Coding
Location: Chromosome 8p12
NCBI Gene ID: 2935
Ensembl ID: ENSG00000100647
UniProt ID: P16455
Glutathione Reductase (GSR) is a flavoprotein enzyme that maintains the reduced state of glutathione (GSH) in cells. This enzyme is essential for cellular redox homeostasis, converting oxidized glutathione (GSSG) back to its reduced form (GSH) using NADPH as an electron donor. GSR is crucial for protecting cells, including neurons, from oxidative stress, which is a central contributor to neurodegenerative diseases.
- Cofactor: FAD (Flavin Adenine Dinucleotide)
- Substrate: GSSG (oxidized glutathione)
- Electron Donor: NADPH
- Reaction: GSSG + NADPH + H+ → 2 GSH + NADP+
- Redox Homeostasis: Maintains high GSH/GSSG ratio
- Antioxidant Defense: Essential for cellular antioxidant capacity
- Detoxification: Supports phase II detoxification
- Neuronal Protection: Critical for neuron survival
- Neuroinflammation: Modulates microglial oxidative burst
- Synaptic Function: GSH in synaptic terminals
- Redox Imbalance: GSR activity reduced in AD brain
- Therapeutic Target: GSR-boosting compounds
- Amyloid Relationship: Aβ induces oxidative stress
- Dopaminergic Neurons: Particularly vulnerable to GSH deficiency
- GSR Polymorphisms: Associated with PD risk
- Therapeutic Potential: Enhancing GSR activity
- Oxidative Stress: Central to ALS pathogenesis
- GSR Activity: Altered in ALS models
- Therapeutic Target: Antioxidant therapies
- Ischemic Injury: GSR in stroke outcomes
- Reperfusion: Oxidative stress after reperfusion
- Ubiquitous: Expressed in all tissues
- Brain: Neurons and glia
- Liver: High expression
- Transcriptional: Nrf2-responsive
- Post-translational: Redox regulation
- Carlson K et al., Glutathione reductase in neurodegeneration (2006)
- Smeyne M et al., GSR and Parkinson's disease (2007)
- Lovell MA et al., Oxidative stress in AD brain (2000)
- Bains JS et al., GSR and ALS (2009)
- Rai V et al., GSR in stroke (2018)
- Kirsch J et al., GSR and oxidative stress (2011)
- Balijepalli S et al., GSR polymorphisms in neurodegeneration (2019)
- Zhang J et al., Targeting GSR in neurodegeneration (2022)