SECOND GENOME DYNAMICS NEUROSCIENCE MEETING: DNA TRANSACTIONS IN THE AGING BRAIN

描述（由申请人提供）：随着美国老龄化人口的增加，我们预计会出现迟发性神经退行性疾病患者的激增，包括阿尔茨海默型痴呆（AD）、各种形式的帕金森病（PD）、多发性梗死、额颞叶、路易体、亨廷顿（HD）和皮层下痴呆，以及各种形式的共济失调。所有这些疾病似乎都与细胞中的基因组改变和DNA修复能力有关，而且它们与大脑老化的生物学关系尚不清楚。我们建议召开一次会议，将衰老的基本过程与DNA修复、基因组不稳定性以及神经和神经退行性疾病的临床方面结合起来。该项目旨在将三组对衰老、DNA修复和神经退化感兴趣的顶尖科学家聚集在一起。这些领域的合并旨在为正常衰老过程如何促进晚发性疾病的发展提供新的见解。目前还没有一个会议能综合这三个领域的进展。因此，提议的会议开辟了新天地。对于大多数神经科学家来说，神经异常主要是根据蛋白质介导的毒性来考虑的。然而，新出现的数据表明，DNA修复能力和链断裂的年龄依赖性改变是与AD、PD和HD等晚发性疾病相关的关键因素。DNA修复和基因组不稳定性的主题已经在会议上进行了典型的讨论，因为它涉及到循环细胞和癌症。然而，已经很清楚的是，DNA中累积病变的影响在终末分化细胞（如神经元）中是不同的，并且随着年龄的变化而变化。相对而言，人们对其机制知之甚少。会议的重点是当前和新兴的主题：与衰老神经元的损伤修复如何正常改变有关，以及(2)DNA修复和基因组不稳定性的改变如何可能导致神经退行性疾病的晚发。我们致力于支持青年科学家，鼓励智力对话，分享思想，并与知名专家讨论当前出现的问题。随着美国老龄化人口的增加，我们预计患有晚发性神经退行性疾病的患者将激增。所有这些疾病似乎都与细胞中的基因组改变和DNA修复能力有关，而且它们与大脑老化的生物学关系尚不清楚。我们建议召开第二届基因组动力学神经科学会议（GDN II），将衰老的基本过程与DNA修复、基因组不稳定性以及神经和神经退行性疾病的临床方面结合起来。该计划旨在汇集三组顶尖科学家：(1)主要研究大脑衰老的基本机制的科学家；(2)主要研究DNA损伤及其修复的科学家；(3)主要研究特定神经退行性疾病的科学家。这些领域的合并旨在对正常衰老过程如何促进晚发性疾病的发展产生新的见解。

DESCRIPTION (provided by applicant): With the increasing size of the aging population in the United States, we anticipate a surge of patients with late-onset neurodegenerative disorders, including dementias of the Alzheimer type (AD), various forms of Parkinson disease (PD), multi-infarct, fronto- temporal, Lewy body, Huntington (HD) and subcortical dementias, and various forms of ataxia. All of these disorders appear to involve genome alterations and DNA repair capacity in cells, and they are coupled to the biology of the aging brain in ways that remain unclear. We propose a meeting that integrates basic processes of aging with those of DNA repair, genomic instability, and clinical aspects of neurological and neurodegenerative disease. The program is designed to bring together three groups of leading scientists with interests in aging, DNA repair, and neurodegeneration. Merging of these fields is intended to develop new insights into in how normal processes of aging contribute to the development of late-onset disease. There is no existing meeting that integrates advances in all three fields. Thus, the proposed meeting breaks new ground. For most neuroscientists, neurological abnormalities have been considered primarily in light of protein-mediated toxicity. However, emerging data implicate both age-dependent alterations in DNA repair capacity and strand breaks as key factors relevant to late onset disease such as AD, PD, and HD. The theme of DNA repair and genomic instability has been typically discussed at meetings as it relates to cycling cells and cancer. It has become clear, however, that impact of accumulating lesions in DNA is different in terminally differentiated cell such as neurons, and changes with age. Relatively little is known about the mechanisms. The meeting focuses on current and emerging topics: relevant to how lesion repair changes normally in aging neurons, and (2) how alterations in DNA repair and genomic instability might contribute to late onset of neurodegenerative disease. We are committed to supporting young scientists and encouraging intellectual dialogue, the sharing of ideas, and discussion of current emerging issues with established experts. Project Narrative With the increasing size of the aging population in the United States, we anticipate a surge of patients with late-onset neurodegenerative disorders. All of these disorders appear to involve genome alterations and DNA repair capacity in cells, and they are coupled to the biology of the aging brain in ways that remain unclear. We propose the Second Genome Dynamics Neuroscience Meeting (GDN II) that integrates basic processes of aging with those of DNA repair, genomic instability, and clinical aspects of neurological and neurodegenerative disease. The program is designed to bring together three groups of leading scientists: (1) those with a primary interest in basic mechanisms of aging in the brain, and (2) those with primary interests in DNA lesions and their repair, and (3) those with interests in specific neurodegenerative diseases. Merging of these fields is intended to develop new insights into how normal processes of aging contribute to the development of late-onset disease.