Optical Imaging of Fly Brains for Neurodegeneration Research

仅在英国就有大约100万人患有神经退行性疾病，而且这个数字还在上升。它们给患有这些毁灭性疾病的个人、他们的亲属和整个经济造成了巨大的负担，尽管进行了所有的研究努力，但目前还没有治愈方法。帕金森症和阿尔茨海默症等疾病之间的一个关键现象是，通常无害的蛋白质开始改变形状、聚集和行为失常，从而对患者大脑中的神经元产生毒性。没有人知道是什么机制导致了这种功能障碍，也不知道如何预防。一个巨大的问题是，目前的工具无法追踪这些蛋白质是如何在活人体内形成有毒结构的。我们在这里提出的是，利用物理学家和遗传学家的专业知识，开发一个新的平台，使我们能够直接研究这些有毒聚集体在活体大脑中的形成，当然不是人类的大脑，而是果蝇的大脑，这些大脑可以用光学显微镜观察，可以作为人类可能发生的模型。如果我们成功地建立了这样一种技术，我们将有一个工具来了解这种疾病，并通过它来测试潜在的药物，以防止有毒结构的形成。

Approximately 1 million people in the UK alone are suffering from neurodegenerative diseases, and the number is rising. They pose a huge burden on individuals suffering from these devastating diseases, their relatives, and the economy as a whole, and despite all research efforts there are currently no cures. A key phenomenon linking diseases such as Parkinsons and Alzheimers is that proteins, which are normally harmless, start to change shape, to aggregate and to misbehave so as to become toxic to the neurones in the patients brains. Nobody knows what mechanisms leads to this dysfunction nor how to prevent it. A huge problem is that one cannot with current tools follow how the proteins form into toxic structures in living individuals. What we propose here is to develop, by drawing on the expertise of physicists and geneticists, a novel platform that will permit us to study the formation of such toxic aggregates directly in living brains, not human brains of course, but the brains of fruit flies, which are amenable to optical microscopes and can serve as models of what might be going on in humans. If we succeed in building such a technology, we would have a tool with which to understand the disease and with which to test potential drugs which prevent the toxic structures from forming.