Evaluation of the kinases responsible for tau toxicity

神经退行性疾病，如阿尔茨海默病？的疾病是极其衰弱和痛苦的。就像老年痴呆症？老年痴呆症主要影响老年人，目前的人口趋势是人口继续长寿，老年痴呆症的影响？s将大幅增加。为了开发更有效的治疗方法，需要了解更多关于疾病的根本原因。它是目前公认的，有一个不正常的积累蛋白质在脑细胞的阿尔茨海默氏症？这导致神经细胞的损失，最终导致痴呆症。许多工作已经确定，一种称为tau的蛋白质是在病变细胞中积累的蛋白质之一。Tau通常对神经细胞功能有重要作用，但在阿尔茨海默病中？一旦得了这种病，这种蛋白质的功能就开始不正常。在疾病状态下，由于异常添加过量的磷酸盐，tau蛋白的化学性质发生了变化。阿尔茨海默病治疗方法发展的一个希望？研究这种疾病的关键是找到阻断将磷酸盐添加到tau蛋白上的酶（称为激酶）的药物。已经鉴定了几种候选激酶，我们现在需要鉴定哪种激酶是病变细胞中毒性tau蛋白形成的主要贡献者。在人类中不可能做到这一点，在小鼠中也很难快速做到。在这个项目中，我们将使用果蝇（果蝇）作为模型系统，在那里我们可以准确和有效地评估哪些激酶负责产生异常磷酸化的tau蛋白。通过确定负责的激酶，我们将能够开发更有效的治疗方法。我们还计划研究是否可以使用果蝇作为检测系统来测试可能减轻阿尔茨海默病病因的药物的有效性。的疾病。由于我们计划开展的工作可能对一种众所周知的疾病的未来治疗产生重大影响，我们将努力通过在我们的网站上展示重大进展，通过同行评议的出版物，并在适当的情况下通过新闻公告，向公众提供我们的工作成果。

Neurodegenerative diseases such as Alzheimer?s disease are extremely debilitating and distressing. As Alzheimer?s disease mainly affects older people and the current demographic trend is towards a population that continues to live longer the impact of Alzheimer?s will increase significantly. To allow more effective treatments to be developed more needs to be understood about the underlying causes of the disease. It is currently recognised that there is an abnormal build-up of protein in the brain cells of Alzheimer?s sufferers which results in the loss of nerve cells which leads ultimately to dementia. Much work has previously established that a protein known as tau is one of the proteins that accumulates in diseased cells. Tau normally has an important role for nerve cell function but in Alzheimer?s disease this protein begins to function abnormally. In the disease state the tau protein that builds up is chemically altered by the abnormal addition of excess amounts of phosphate. One hope for the development of treatments for Alzheimer?s disease is to find drugs that block the enzymes (known as kinases) that add this phosphate onto the tau protein. Several candidate kinases have been identified and we now need to identify which of the kinases is a major contributor to the formation of toxic tau protein in diseased cells. It is not possible to do this in human and is also difficult to do rapidly in mouse. In this project we will use the fruit fly (Drosophila) as a model system where we can accurately and efficiently evaluate which of the kinases are responsible for the production of abnormally phosphorylated tau. By identifying the kinases that are responsible we will enable the development of more effective therapies. We also plan to investigate whether we can use Drosophila as an assay system to test the effectiveness of drugs that may alleviate the causes of Alzheimer?s disease. As the work that we plan to do may have significant implications for the future treatment of a well known disease we will endeavour to make the results of our work available to the general public by presenting significant advances on our website, through peer-reviewed publications and where appropriate through press announcements.