PET Markers of Oligomeric Misfolded Proteins in Neurodegenerative Disorders

神经退行性疾病中寡聚错误折叠蛋白的 PET 标记

基本信息

批准号：
EP/P008224/1
负责人：
Franklin Aigbirhio
金额：
$ 132.75万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FP008224%2F1
关键词：
PET Markers Oligomeric Misfolded Proteins

项目摘要

A common feature of all dementias e.g. Alzheimer's, Parkinson's and Huntington's diseases are the presence of specific proteins in the brain, which due to having abnormal structures, accumulate into increasingly large assemblies and fibrils. These structures, which are present in many regions of the brain, are considered to be toxic and damage brain cells, leading to the symptoms of dementia. Using the clinical brain imaging technique of Positron Emission Tomography (PET) combined with injecting into patients chemical probes which selectively bind to these assembles we can now visualize the presence and distribution of some of these toxic proteins. However, with the present range of these chemical probes we can only image the late stages of these assemblies when most of the brain damage has occurred and so too late for effective drugs therapies. Therefore our aim is to develop next generation chemical probes that can image the earlier stages and structures of these abnormal proteins when they are considered most toxic and hence cause the most damage to brains cells. This would then create a powerful means for earlier more accurate diagnosis of dementia and a means of evaluating the new types of drugs that are been developed that target these assemblies. To discover and develop these new chemical probes, will apply chemical screening methods, medicinal chemistry, radiochemistry and biological assessments. The chemical probes with appropriate properties arising from this project we would then take forward with additional funding for human imaging studies.

所有痴呆症的共同特征，例如阿尔茨海默氏症，帕金森氏症和亨廷顿的疾病是大脑中特定蛋白质的存在，由于结构异常，它们会积聚成越来越大的组件和原纤维。这些结构存在于大脑的许多区域，被认为是有毒的，会损害脑细胞，导致痴呆症的症状。使用正电子发射断层扫描（PET）的临床脑成像技术，并将注射到患者的化学探针中，这些探针有选择地与这些组装结合，我们现在可以看到这些有毒蛋白的某些毒素的存在和分布。但是，在这些化学探针的当前范围内，我们只能在大部分脑损伤发生时，就可以对这些组件的后期进行成像，因此对于有效的药物疗法而言，为时已晚。因此，我们的目的是开发下一代化学探针，这些化学探针可以在被认为是最有毒的情况下对这些异常蛋白的较早阶段和结构进行成像，从而对大脑细胞造成最大的损害。然后，这将创建一种强大的手段，以更早地准确诊断痴呆症，并评估开发出针对这些组件的新型药物的方法。为了发现和开发这些新的化学探针，将采用化学筛查方法，药物化学，放射化学和生物学评估。然后，我们将获得具有适当特性的化学探测器，然后我们将通过额外的资金进行人类影像学研究。