Significance: Thioredoxin 1 (Trx1) is a ubiquitous protein that is found in organisms ranging from prokaryotes to eukaryotes. Trx1 acts as reductases in redox regulation and protects proteins from oxidative aggregation and inactivation. Trx1 helps the cells to cope with various environmental stresses and inhibits programmed cell death. It is beneficial to neuroregeneration and resistance against oxidative stress-associated neuron damage. Trx1 also plays important roles in suppressing neurodegenerative disorders. Recent Advances: Trx1 is a redox regulating protein involved in neuronal protection. According to a previous study, Trx1 expression is increased by nerve growth factor (NGF) and necessary for neurite outgrowth of PC12 cells. Trx1 has been shown to promote the growth of neurons. Trx1 knockout or knockdown has the worse impact on cell viability and survival. Critical Issues: Trx1 has functions in central nervous system. Trx1 plays the defensive roles against oxidative stress in neurodegenerative diseases. Future Directions: In this review, we focus on the structure of Trx1 and basic functions of Trx1. Trx1 plays a neuroprotective role by suppressing endoplasmic reticulum stress in Parkinson's disease. Neurodegenerative diseases have no cure and carry a high cost to the health care system and patient's families. Trx1 may be taken as a new target for neurodegenerative disorder therapy. Further studies of the Trx1 roles and mechanisms on neurodegenerative diseases are needed. Antioxid. Redox Signal. 36, 1023-1036.
Keywords: 1-methyl-4-phenyl-1236-tetrahydropyridine; 1-methyl-4-phenylpyridinium; Alzheimer's disease; Parkinson's disease; neurodegenerative diseases; thioredoxin 1; thioredoxin reductases.