Thioredoxins comprise a class of redox proteins that are conserved in all organisms from lower prokaryotes to humans and function as general protein disulfide reductases. Several forms of thioredoxins, confined to different subcellular localizations, have been identified in eukaryotic cells. A number of functions are assigned to thioredoxins mainly dependent on their redox abilities such as modulation of transcription factor DNA binding activity, antioxidant defense, regulation of cell growth and apoptosis, co-cytokine activity, etc. In addition, thioredoxins have been reported to be involved in a plethora of pathological situations such as neurodegenerative diseases, cardiac arrest, diabetes, infertility or aging. In spite of the clear connection of the different thioredoxins with numerous diseases, we are still far from unravelling the cellular and biochemical mechanisms in which thioredoxins are involved. This is mostly due to the absence of an appropriate animal model as knocking-out the genes coding for thioredoxins results in embryonic lethal phenotypes both in mice and flies.

An alternative to overcome this problem is the use of the nematode Caenorhabditis elegans whose applicability as experimental model is sustained by the remarkable success that this invertebrate has met during the last few years in recapitulating several human diseases of different etiology. Furthermore, the presence of several thioredoxin genes in the C. elegans genome, with clear orthologs in mammals, provides an excellent framework to further investigate the functions of the different thioredoxins and its use to solve major questions in the biology of these proteins. It is in this promising scenario where we have initiated a project aiming to decipher, by a genetic approach, the function of the thioredoxin systems in the model organism Caenorhabditis elegans expecting to provide relevant information about the significance of these proteins and their potential implications, at the molecular level, in several of the most important pathologies affecting humans. In this context, initial results in our group have resulted in the identification in C. elegans of the first neuron-specific thioredoxin ever reported in metazoans, thus paving the way to use this organism to study the role of thioredoxins in nervous system physiology and pathology.