Stem Cells, Prion Proteins and Alzheimer's Diseases: A Prion Chemical Biology Network (PCBNet)

PrPC是位于20号染色体上的人PrNP基因编码的一种膜锚定糖蛋白。PrPC在神经细胞中广泛表达，但表达水平明显高于神经细胞。它在脊椎动物中高度保守，已被证明与许多发育过程和许多正常和异常情况有关，包括记忆、神经保护、传染性海绵状脑病(TSE)、阿尔茨海默病(AD)和癌症等。不幸的是，尽管研究委员会和政府投入了大量资金，但上述正常或异常情况的确切机制尚未得到证实。造成这种认识不足的原因之一是在普恩化学生物学研究方面缺乏突破。在过去的十年中，Prion的研究一直由联合资助者(EPSRC、BBSRC、MRC、卫生部、DEFRA和其他主要研究委员会和慈善机构)协调，其职权范围非常广泛，主要集中在TSE研究。其结果是，许多其他与Prion相关的研究领域协调得不太好，资金严重不足。在这里，我们建议建立一个Prion化学生物学网络，以促进多学科的合作研究，支持Prion蛋白在干细胞和发育以及AD等与衰老相关的神经退行性疾病中的作用，从而提供一个平台，将基础研究快速转化为Prion相关的药物发现和干预，转向再生医学和抗击神经退行性疾病。建立强大的联合体以吸引更多的未来研究资金将是这个拟议网络的关键成果。该网络将寻求推动对两个与老龄化社会和个性化医学相关的相对较新的领域的普恩化学生物学研究，以近年来在可传播海绵状脑病(TSE)研究中发展的理解、技术和设施方面的进展为基础：1)普恩蛋白在干细胞行为和功能以及胚胎发育中的正常生理作用；2)普恩蛋白在衰老和神经退行性疾病(如阿尔茨海默病(AD)和普恩蛋白变性疾病)中的作用。

Cellular prion protein, PrPC, is a membrane-anchored glycoprotein encoded by the human Prnp gene located on chromosome 20. PrPC is expressed ubiquitously, but at significantly higher levels in neuronal cells. It is highly conserved across vertebrates and has been shown to exhibit a diverse range of biological activities associated with many developmental processes and a number of normal and abnormal conditions including memory, neuroprotection, Transmissible spongiform encephalopathy (TSE), Alzheimer's diseases (AD) and cancer etc. Unfortunately, the exact mechanisms for each of the above normal or abnormal conditions are yet to be confirmed despite significant investment from research councils and government. Contributing to this lack of understanding is a dearth of breakthroughs in prion chemical biology research. Prion research over the past decade has been coordinated by joint funders (EPSRC, BBSRC, MRC, and Department of Health, DEFRA and other major research councils and charity) with a very broad remit mainly focusing on TSE research. As a result, many other prion related research areas are less well coordinated and severely underfunded. Here we propose to establish a prion chemical biology network to promote multidisciplinary collaborative research underpinning the role of prion protein in stem cell and development and ageing-related neurodegenerative diseases such as AD, so as to provide a platform for the rapid translation of underpinning research into prion related drug discovery and intervention towards regenerative medicine and combating neurodegenerative disease. Building up strong consortia to attract more future research funding will be the key outcome of this proposed network. The network will seek to drive prion chemical biology research into two relatively new areas of relevance to the ageing society and in personalised medicine, building on the advances in understanding, skills and facilities developed in the study of transmissible spongiform encephalopathy (TSE) over recent years: 1)The normal physiological role of prion protein in the behaviour and function of stem cells and in embryonic development; 2)The role of prion protein in ageing and neurodegenerative diseases, e.g. Alzheimer's disease (AD) and TSE.