NEURON SURVIVAL IN CHAGAS DISEASE

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DESCRIPTION (Adapted from the Investigator's Abstract): Chagas disease, caused by the protozoan Trypanosoma cruzi, progresses through 3 stages: 1) acute disease, characterized by robust parasite growth, immunological disturbances, and peripheral neural degeneration; 2) indeterminate phase, asymptomatic and featuring extensive regeneration of neurons; and 3) chronic phase, characterized by immunological alterations and pronounced degeneration of neurons in the heart and GI tract. Most patients remain asymptomatic and with signs of neuronal regeneration for decades, but for enigmatic reasons, some (<10 percent) undergo extensive degeneration of neurons (along with immunological disturbances) to progress to the fatal chronic disease. Recent studies may provide insights into the molecular basis of neuronal changes in Chagas disease. Picomolar levels of the T. cruzi trans-sialidase (TS) were found to protect several types of neuronal cells from undergoing apoptotic death. What's more, TS synergized with two human neurotrophic cytokines, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), to promote neuronal survival. Therefore, the possibility exists that neuronal regeneration in Chagas disease results from the collaboration of TS with CNTF or LIF. In addition, and most interesting, because about 2.5 percent and 25 percent of normal people are homozygous and heterozygous, respectively, for a null mutation in the CNTF gene, the possibility exists that individuals bearing mutation of this neurotrophic cytokine are more prone to develop extensive degeneration of neurons if infected with T. cruzi and thus to progress to chronic Chagas' disease.