Unifying Mechanisms of Neurological Disorders: Scientific, Translational, and Cli

简介（由申请人提供）：第26届国际欧洲毒理学会议（NEUROTOX 26）将于2010年6月6日至11日在俄勒冈州波特兰举行，会议主题为“神经系统疾病的统一机制”。会议地点是波特兰万豪市中心滨水酒店，会议价格已大幅降低。国际神经毒理学会议是一个一年一度的活动，它关注的是一个及时和具有煽动性的主题，这个主题有很大的可能性通过跨学科的国际科学家小组在这个建立的会议系列的独特“氛围”和有组织的形式来推进该领域，同时提供了一个展示与神经毒理学一般跨学科领域相关的新数据的机会。提案中确定的具体目标将通过举行一次为期4天的会议来实现，其形式与本系列以前的会议类似，已被证明非常成功。每个会议都有自己独特的“特别之处”，包括辅导课、专题讨论会、平台会议、研讨会、小组讨论、圆桌会议、辩论、海报会议、博士生前和博士后学生竞赛和颁奖宴会、社交活动以及促进网络和指导的新方法。NEUROTOX 26将不仅仅是一个展示数据的场合。它还将通过提供一个公认的场所，将人类、实验动物、方法学和流行病学研究结合起来，使以前没有联系的研究人员能够聚集在一起，并在那里出现共同点。传统上，神经毒理学会议特别强调培养、促进和奖励博士生和博士后学生以及年轻的研究人员。额外的努力延伸到指导学生，并帮助他们与该领域的领导者建立联系。主题理由：在过去几年中，对神经系统疾病和失调的研究已经发展到认识到，在看似不同的疾病状态中往往存在重叠的相似之处。尽管遗传因素长期以来一直是神经系统疾病的主要焦点，但在各种神经系统疾病中，识别涉及的单个基因的情况超过一小部分已被证明是困难的。这些发现使人们认识到环境因素或基因-环境相互作用可能在疾病发病机制中起关键作用。因此，了解导致神经功能障碍表现的共同机制以及遗传和环境因素有可能为神经疾病的病理生理学提供见解，并最终导致更好的疾病预防和治疗。为了实现了解神经系统疾病的共同机制和贡献者的目标，我们建议召开一次题为“神经系统疾病的统一机制”的会议。通过这次会议，我们计划汇集临床医学、基础科学、毒理学和转化研究方面的专家，探讨神经系统疾病的共同机制，目的是促进历史上没有显著程度相互作用的群体之间的相互作用和知识转移。我们选择将重点放在与许多神经系统疾病状态相关的两个主要常见机制和三个新兴研究领域，这些研究领域有可能从增加关注中受益。首先，我们将探讨线粒体功能障碍的作用，线粒体功能障碍是几种破坏性神经系统疾病的标志，如帕金森病、阿尔茨海默病、亨廷顿舞蹈症和ALS。本次会议将评估有关线粒体功能在疾病中的突出问题，包括线粒体功能障碍在发病机制中的作用，环境因素和基因-环境相互作用的作用，以及线粒体功能如何靶向治疗干预。第二个主要的共同机制将集中在蛋白质聚集和错误折叠在神经系统疾病中的作用。蛋白质聚集和错误折叠与多种遗传和特发性神经系统疾病有关。然而，目前关于这一过程是疾病过程的原因还是结果存在争议。本次会议将汇集神经病理学、临床医学和基础研究人员的专家，评估蛋白质聚集和错误折叠在神经系统疾病中的作用，以及通过检查影响这些途径的共同机制可以收集到的与发病机制和治疗有关的信息。我们选择关注的三个新兴领域包括渠道病变、性别和表观遗传学。通道病被认为在癫痫、慢性疼痛和偏头痛中起重要作用。尽管大多数研究的焦点都集中在通道蛋白遗传改变的作用上，但多种环境毒物靶向离子通道，这表明环境暴露可能导致通道病变。国际移民组织的报告《性重要吗》（2001年）强调，由于男女在疾病模式以及对治疗方法和药物的反应方面存在巨大差距，有必要检查研究事业中男女反应的差异。本次研讨会旨在举例说明目前对环境化学易感性的性别差异的认识，并提出对环境暴露、性别和神经系统疾病发展之间关系的见解。最后，我们将探讨表观遗传改变在神经系统疾病中的作用。新出现的证据表明，在发育的关键时期，环境暴露导致的表观遗传改变可能在神经发育障碍中起重要作用。本次会议旨在评估这方面的知识现状，并确定涉及表观遗传改变的常见机制，这些机制可能为疾病发病机制和最终的治疗干预提供见解。

DESCRIPTION (provided by applicant): The Twenty-Sixth International Eurotoxicology Conference (NEUROTOX 26) addressing the theme of "Unifying Mechanisms of Neurological Disorders" will be held June 6-11, 2010 in Portland, Oregon. The meeting location is the Portland Marriott Downtown Waterfront Hotel where greatly reduced conference rates have been negotiated. The International Neurotoxicology Conference is an annual event that focuses on a timely and provocative theme that has a high probability of advancing the field by being addressed by an interdisciplinary, international group of scientists in the unique "atmosphere" and organized format of this established Conference Series - while at the same time providing an opportunity for presenting new data related to the general interdisciplinary field of neurotoxicology. The Specific Aims identified in the proposal will be accomplished by conducting a 4 day conference according to a varied format similar to previous conferences in this series which has proven to be highly successful. Each conference has its own "special touch" unique to the venue and consists of Tutorials, Symposia, Platform Sessions, -Workshops, Panel Discussions, Roundtables, Debates, Poster Session, Pre- and Postdoctoral Student Competition and Awards Banquet and social events as well as novel approaches to facilitate networking and mentoring. NEUROTOX 26 will not be simply an occasion to present data. It will also coalesce human, experimental animal, methodological, and epidemiological research by offering a well-recognized venue where previously unconnected investigators can come together and where commonalties can emerge. Traditionally the Neurotoxicology Conference places special emphasis on nurturing, promoting and rewarding pre- and post-doctoral students and young investigators. Extra effort is extended to mentor students and help them network with the leaders in the field. Justification for the Theme: Over the past several years, research into neurological disease and disorders has evolved to recognize that there are often overlapping similarities in seemingly different disease states. Although genetic factors have long been a primary focus in neurological disease, identification of single genes involved in more than a small fraction of cases in a variety of neurological disorders has proven difficult. These findings have led to the emerging recognition that environmental factors or gene-environment interactions are likely to play a pivotal role in disease pathogenesis. Thus, understanding common mechanisms and genetic and environmental factors that contribute to manifestation of neuronal dysfunction has the potential to provide insight into the pathophysiology of neurological disorders and ultimately lead to better prevention and treatment of disease. In order to accomplish the goal of understanding common mechanisms and contributors to neurological disease, we are proposing to convene a conference entitled "Unifying Mechanisms of Neurological Disorders". Through this conference, we plan to bring together experts in clinical medicine, basic science, toxicology, and translational research to explore common mechanisms of neurological disease with the goal of facilitating interactions and the transfer of knowledge between groups that have not historically interacted to a significant degree. We have chosen to focus on two major common mechanisms associated with a number of neurological disease states and three emerging areas of research that have the potential to benefit from increased focus. First, we will explore the role of mitochondrial dysfunction, which is a hallmark of several devastating neurological disease such as Parkinson's, Alzheimers, Huntington's, and ALS. The salient questions relating to mitochondrial function in disease to be assessed in this session will include the role of mitochondrial dysfunction in pathogenesis, the role of environmental factors and gene-environment interactions, and how mitochondrial function can be targeted for therapeutic intervention. The second major common mechanism of focus will be on the role of protein aggregation and misfolding in neurological disease. Protein aggregation and misfolding have been linked to a variety of neurological disorders, both genetic and idiopathic in origin. However, there is currently controversy as to whether this process is a cause or consequence of the disease process. This session will bring together experts in neuropathology, clinical medicine, and basic researchers to evaluate the role of protein aggregation and misfolding in neurological disease and what information relating to pathogenesis and treatment that can be gleaned from examining common mechanisms affecting these pathways. The three emerging areas that we have chosen for focus include channelopathies, gender, and epigentics. Channelopathies are thought to play an important role in epilepsy, chronic pain, and migraine. Although most of the focus has been on the role of genetic alterations in channel proteins, a variety of environmental toxicants target ion channels, which suggests the potential for environmental exposures to contribute to channelopathies. The IOM report, "Does Sex Matter" (2001) emphasized the need for examining differences between male and female responses in the research enterprise because of wide gaps between males and females in disease patterns and in response to therapeutic practices and drugs. This symposium is designed to exemplify both current knowledge of sex differences in environmenal chemical vulnerability and to propose insight into the relationship between the environmental exposures, gender, and the development of neurological disease. Finally, we will explore the role of epigenetic alterations in neurological disorders. Emerging evidence suggests that epigenetic alterations resulting from environmental exposures during critical periods of development may play a significant role in neurodevelopmental disorders. This session is designed to assess the current state of knowledge in this and identify common mechanisms involving epigenetic alterations that may provide insight into disease pathogenesis and ultimately, therapeutic intervention. PUBLIC HEALTH RELEVANCE: The health relatedness of this application is that he results of this conference will contribute to a fuller understanding of the true risk posed by exposure to a variety of neurotoxicants on human neurological diseases or disorders. Exposure to a variety of neurotoxicants has been associated with characteristic derangements of nervous system function, some fleeting in nature and others virtually permanent. Furthermore, exposure to neurotoxicants has been hypothesized to play a role in the development of many neurological diseases and disorders. NEUROTOXICOLOGY 26 will focus on common mechanisms in neurological disease and the role of environmental exposures and gene-environment interactions in the development of neurological disease and disorders.