Anastasis in age-related neurodegeneration

与年龄相关的神经退行性疾病，包括阿尔茨海默病、帕金森氏病和各种 一些不太常见的疾病，影响到大量个人，而且基本上无法治疗。一种新的机制 疾病代表着尚未开发的治疗开发潜力。在这里，我们建议Anastsis(源自希腊语， 从末端caspase激活中恢复，代表了一种新的诱导机制。 年龄依赖性神经退行性疾病中的神经元死亡。我们提供的初步数据来自于 亚历山大病的模型，一种原发星形胶质细胞介导的神经退行性疾病的范例，表明 阿纳斯塔西病会导致神经元死亡。我们进一步利用了有价值的基因组规模的基因筛查 在亚历山大病果蝇体内模型中进行研究以确定控制胶质细胞转移的机制 和继发性非细胞自主神经退行性变。然后，我们测试Anastsis贡献的假设 与阿尔茨海默病和相关疾病相关的果蝇模型中的神经退行性变。最后，我们 检查牵张症的小鼠模型，寻找与血管转移症相关的标志物。我们的研究有可能 确定一种新的机制来调节衰老相关疾病中的神经退行性变 发展减缓神经性衰退的发病和进展的方法的机会。

Age-dependent neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and a variety of less common disorders, affect large numbers of individuals and are largely untreatable. Novel mechanisms of disease represent untapped potential for therapy development. Here we propose that anastasis (from the Greek, “rising from the dead”), or recovery from terminal caspase activation, represents a new mechanism inducing neuronal death in age-dependent neurodegenerative diseases. We present preliminary data derived from models of Alexander disease, an exemplar primary astrocyte mediated neurodegenerative disorder, to suggest that that anastasis drives neuronal death. We further capitalize on a valuable genome-scale genetic screen performed in an in vivo Drosophila model of Alexander disease to define mechanisms controlling glial anastasis and secondary non-cell autonomous neurodegeneration. We then test the hypothesis that anastasis contributes to neurodegeneration in Drosophila models of relevant to Alzheimer’s disease and related disorders. Finally, we examine mouse models of tauopathy for markers associated with anastasis. Our studies have the potential to define a new mechanism mediating neurodegeneration in aging-related disorders with accompanying opportunities for development of approaches to slow the onset and progression of neurological decline.