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

神经系统疾病的统一机制：科学、转化和气候

• 批准号: 7920278
• 负责人: Joan Marie Cranmer
• 金额: $ 4万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920278
• 关键词: Address; Affect; Animals; Area; Award; Basic Science; Characteristics; Chemicals; Clinical Medicine; Data; Development; Disease; Educational workshop; Environmental Exposure; Environmental Risk Factor; Epidemiology; Epigenetic Process; Epilepsy; Event; Exposure to; Female; Functional disorder; Gender; Genes; Genetic; Glean; Goals; Health; Human; Huntington Disease; International; Ion Channel; Knowledge; Lead; Link; Location; Mediation; Mentors; Migraine; Mitochondria; Mutation; Nature; Nervous System Physiology; Neurodevelopmental Disorder; Neuronal Dysfunction; Neurotoxins; Oregon; Parkinson Disease; Pathogenesis; Pathway interactions; Pattern; Pharmaceutical Preparations; Play; Postdoctoral Fellow; Prevention; Probability; Process; Proteins; Reporting; Research; Research Personnel; Rewards; Risk; Role; Scientist; Series; Sex Characteristics; Students; Therapeutic; Therapeutic Intervention; Time; Touch sensation; Toxic Environmental Substances; Toxicology; Translational Research; chronic pain; critical period; design; gene environment interaction; insight; male; meetings; mitochondrial dysfunction; nervous system disorder; neuropathology; neurotoxicology; novel strategies; planetary Atmosphere; posters; protein aggregation; public health relevance; response; sex; social; symposium

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.

描述（由申请人提供）：第二十六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，主题为“神经系统疾病的统一机制”。会议地点是波特兰市中心海滨万豪酒店，会议价格已协商大幅降低。国际神经毒理学会议是一项年度活动，重点关注及时且具有挑衅性的主题，跨学科的国际科学家小组在这一既定会议系列的独特“氛围”和组织形式中进行演讲，极有可能推动该领域的发展- 同时提供展示与神经毒理学跨学科领域相关的新数据的机会。该提案中确定的具体目标将通过举行为期 4 天的会议来实现，会议的形式与本系列之前的会议类似，已被证明非常成功。每个会议都有其独特的场地特色，包括教程、研讨会、平台会议、研讨会、小组讨论、圆桌会议、辩论、海报会议、博士前和博士后学生竞赛以及颁奖晚宴和社交活动作为促进网络和指导的新颖方法。 NEUROTOX 26 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，让以前没有联系的研究人员可以聚集在一起，并可以出现共同点。传统上，神经毒理学会议特别强调培养、促进和奖励博士前、博士后和年轻研究人员。我们还付出额外的努力来指导学生并帮助他们与该领域的领导者建立联系。该主题的理由：在过去的几年中，对神经系统疾病和紊乱的研究已经发展到认识到看似不同的疾病状态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，但事实证明，识别与各种神经系统疾病的一小部分病例有关的单个基因很困难。这些发现使人们逐渐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发挥关键作用。因此，了解导致神经元功能障碍表现的常见机制以及遗传和环境因素有可能深入了解神经系统疾病的病理生理学，并最终更好地预防和治疗疾病。为了实现了解神经系统疾病的常见机制和影响因素的目标，我们提议召开一次题为“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常见机制，目的是促进历史上没有重大互动的群体之间的互动和知识转移。程度。我们选择关注与许多神经系统疾病状态相关的两个主要常见机制以及三个有可能从增加关注中受益的新兴研究领域。首先，我们将探讨线粒体功能障碍的作用，线粒体功能障碍是帕金森病、阿尔茨海默病、亨廷顿舞蹈病和肌萎缩侧索硬化症等多种毁灭性神经系统疾病的标志。本次会议将评估与疾病中线粒体功能相关的突出问题，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，以及如何针对线粒体功能进行治疗干预。第二个主要的共同关注机制是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神经系统疾病有关，包括遗传性和特发性。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，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常见机制可以收集哪些与发病机制和治疗相关的信息。我们选择重点关注的三个新兴领域包括通道病、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发挥重要作用。尽管大多数关注点都集中在通道蛋白基因改变的作用上，但多种环境毒物都以离子通道为目标，这表明环境暴露可能导致通道病。 IOM 报告《性别重要吗》（2001 年）强调，由于男性和女性在疾病模式以及对治疗实践和药物的反应方面存在巨大差异，因此有必要在研究企业中检查男性和女性反应之间的差异。本次研讨会旨在举例说明当前对环境化学脆弱性的性别差异的了解，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。新的证据表明，发育关键时期环境暴露引起的表观遗传改变可能在神经发育障碍中发挥重要作用。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，这些机制可能有助于深入了解疾病发病机制并最终提供治疗干预。 公共健康相关性：本申请的健康相关性在于，本次会议的结果将有助于更全面地了解接触各种神经毒物对人类神经系统疾病或紊乱造成的真正风险。接触各种神经毒物与神经系统功能的特征性紊乱有关，有些是短暂的，有些则是永久性的。此外，假设接触神经毒物在许多神经系统疾病和病症的发展中发挥作用。神经毒理学 26 将重点关注神经系统疾病的常见机制以及环境暴露和基因-环境相互作用在神经系统疾病和紊乱发展中的作用。