NEURON SURVIVAL IN CHAGAS DISEASE

描述（改编自研究者摘要）：恰加斯病，由 由原生动物克氏锥虫，进展通过3个阶段：1）急性 疾病，其特征是寄生虫生长旺盛，免疫紊乱， 和周围神经变性; 2）不确定阶段，无症状， 以神经元的广泛再生为特征;和3）慢性期， 其特征在于免疫学改变和 心脏和胃肠道的神经元。大多数患者无症状， 神经元再生的迹象，但由于神秘的原因，一些 （<10%）经历广泛的神经元变性（沿着 免疫紊乱）发展为致命的慢性疾病。 最近的研究可能会提供深入了解神经元的分子基础， 查加斯病的变化。皮摩尔水平的T.克氏转唾液酸酶 (TS)可以保护几种类型的神经细胞免受 凋亡性死亡更重要的是，TS与两种人类神经营养素 细胞因子、睫状神经营养因子和白血病抑制因子 (LIF)促进神经元存活。因此，存在这样的可能性， 恰加斯病的神经元再生来自TS的合作 CNTF或LIF。此外，最有趣的是， 25%的正常人分别是纯合子和杂合子， 对于CNTF基因中的无效突变，存在个体 携带这种神经营养细胞因子突变的人更容易发展为 感染T. cruzi，因此， 发展成慢性恰加斯病

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.