Proteomic Profiles in Human Temporal Lobe Epilepsy

人类颞叶癫痫的蛋白质组学特征

• 批准号: 7142814
• 负责人: NIHAL C DE LANEROLLE
• 金额: $ 22.28万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7142814
• 关键词: clinical research; genes; human; partial seizure; proteins; proteomics; temporal lobe /cortex disorder

DESCRIPTION (provided by applicant): Epilepsy affects about 2.5 million people in the USA and 40 million worldwide. Of this population 40% are patients with temporal lobe Epilepsy (TLE). In approximately 45% of those with TLE, seizures cannot be well controlled by available medications. Surgery helps a proportion of these patients, but remains a costly procedure with a risk of morbidity. The molecular mechanisms of TLE are not yet fully elucidated, but if better known could provide new avenues for the treatment and/or cure of this disease. Recent developments in methods for high throughput screening of gene (genomics) and protein (proteomics) expression hold promise of more rapid progress in unravelling these molecular mechanisms. We have begun to identify various genes and pathways associated with the pathophysiology of epileptic brain foci from TLE patients supported by a recently received R21. However, gene expression analyses do not by themselves provide reliable information on the actual proteins encoded by identified genes. A single gene can encode many different protein species due to differences in editing and splicing, and their products may show post- translational modification. In this proposal we propose to analyze the proteome in hippocampal seizure foci, to complement genomic studies in progress. In these studies we will use 2-DIGE analyses to identify the protein profile that characterizes mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE). In patients with paradoxical temporal lobe epilepsy (PTLE), where only one in two patients experience seizure free status after surgery, proteomic profiles will be compared with surgical outcome, to elucidate the proteome of the poor responders, as a means to developing a presurgical molecular diagnosis of this group. These studies are essential to identify molecules unique to TLE, which will be the candidates for study in future research that explores their role(s) in seizure mechanisms.

描述（由申请人提供）： 癫痫症影响美国约 250 万人，全球约 4000 万人。该人群中 40% 是颞叶癫痫 (TLE) 患者。大约 45% 的 TLE 患者无法通过现有药物很好地控制癫痫发作。手术对部分患者有帮助，但仍然是一种昂贵的手术，并且存在发病风险。 TLE 的分子机制尚未完全阐明，但如果更好地了解，可以为治疗和/或治愈该疾病提供新途径。基因（基因组学）和蛋白质（蛋白质组学）表达高通量筛选方法的最新发展有望在阐明这些分子机制方面取得更快的进展。我们已经开始从最近收到的 R21 的支持下，识别与 TLE 患者癫痫脑灶病理生理学相关的各种基因和通路。然而，基因表达分析本身并不能提供有关已识别基因编码的实际蛋白质的可靠信息。由于编辑和剪接的差异，单个基因可以编码许多不同的蛋白质种类，并且它们的产物可能表现出翻译后修饰。在本提案中，我们建议分析海马癫痫病灶中的蛋白质组，以补充正在进行的基因组研究。在这些研究中，我们将使用 2-DIGE 分析来鉴定表征内侧颞叶癫痫伴海马硬化 (MTLE) 的蛋白质谱。在矛盾颞叶癫痫 (PTLE) 患者中，只有二分之一的患者在手术后经历无癫痫发作状态，蛋白质组谱将与手术结果进行比较，以阐明反应不佳者的蛋白质组，作为对该组进行术前分子诊断的一种手段。这些研究对于识别 TLE 独特的分子至关重要，这些分子将成为未来研究的候选者，探索它们在癫痫发作机制中的作用。