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Establishment of the nematode Caenorhabditis elegans as a novel platform to study the implications of thioredoxins in nervous system function and agingThe thioredoxin protein family is involved in various cellular processes, such as the modulation of apoptosis, stress-resistance and aging. More importantly, thioredoxins have been implicated in a wide variety of pathologies, such as cancer, arteriosclerosis and cardiovascular disease, in addition to neuronal disorders like Alzheimer's and Parkinson's diseases. Despite the clear connection of thioredoxins to numerous human diseases, there is still a fundamental lack of information at the mechanistic and regulatory levels, mostly due to the absence of appropriate mammalian animal models. Therefore, we intend to characterize the function of the thioredoxin system in C. elegans. We want to use the worm as an experimental platform to study the molecular roles of thioredoxins, with a particular focus on their involvement in the development and function of the nervous system and in aging. We have provided evidence for the first neuron-specific expression pattern of a thioredoxin family member in any metazoan organism. The C. elegans gene trx-1 encodes a thioredoxin that is expressed in the ciliated sensory neuron ASJ. A mutant worm strain carrying a null allele of the trx-1 gene displays a reproducible decrease in lifespan when compared to wild type. We have also found a novel connection between the biology of trx-1 and the insulin signaling pathway, implicating trx-1 in mechanisms governing energy homeostasis in the worm. The identification and initial characterization of trx-1, therefore paves the way to study the thioredoxin system in C. elegans. Consequently, the use of C. elegans as an experimental model to determine the in vivo function of the thioredoxin system is anticipated to greatly contribute to the effective and fast modeling of nervous system physiology, pathology and aging. |
