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规模的增加，我们预期患有迟发性神经退行性疾病的患者激增，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）和皮质下痴呆以及各种形式的共济失调。所有这些疾病似乎都涉及细胞中的基因组改变和DNA修复能力，并且它们以尚不清楚的方式与衰老大脑的生物学相关联。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相结合。该计划旨在汇集三组对衰老，DNA修复和神经退行性疾病感兴趣的领先科学家。这些领域的合并旨在对正常衰老过程如何促进迟发性疾病的发展提出新的见解。目前还没有一次会议综合了所有三个领域的进展。因此，拟议的会议开辟了新的领域。对于大多数神经科学家来说，神经系统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迟发性疾病（如AD、PD和HD）相关的关键因素。DNA修复和基因组不稳定性的主题通常在会议上讨论，因为它与循环细胞和癌症有关。然而，已经清楚的是，DNA中累积损伤的影响在终末分化细胞如神经元中是不同的，并且随着年龄而变化。对这些机制的了解相对较少。会议重点关注当前和新出现的主题：与衰老神经元中损伤修复如何正常变化相关，以及（2）DNA修复和基因组不稳定性的改变如何导致神经退行性疾病的迟发性。我们致力于支持青年科学家，鼓励知识对话，分享想法，并与知名专家讨论当前出现的问题。随着美国老龄化人口规模的增加，我们预计迟发性神经退行性疾病患者会激增。所有这些疾病似乎都涉及细胞中的基因组改变和DNA修复能力，并且它们以尚不清楚的方式与衰老大脑的生物学相关联。我们建议第二次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相结合。该计划旨在汇集三组领先的科学家：（1）对大脑衰老的基本机制感兴趣的人，（2）对DNA损伤及其修复感兴趣的人，以及（3）对特定神经退行性疾病感兴趣的人。这些领域的合并旨在对正常衰老过程如何促进迟发性疾病的发展提出新的见解。

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.