STUDY OF D-ASPARTATE ACCUMULATION IN AGING BRAIN

衰老大脑中 D-天门冬氨酸积累的研究

• 批准号: 3115197
• 负责人: EUGENE H MAN
• 金额: $ 12.01万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115197
• 关键词: Alzheimer's disease; Parkinson's disease; aging; aminoacid metabolism; aspartate; brain metabolism; calcium metabolism; dementia; drug abuse; high performance liquid chromatography; human tissue; myelin; postmortem; racemization

This program is designed to determine the neurophysiological, biochemical, pathological and anatomical implications of the accumulation of D-aspartate with age in the protein of human brain white matter, a phenomenon recently discovered in this laboratory. The steady accumulation of D-aspartic acid, presumed to result from racemization of the common L-acid, may be related to diseases and dysfunctions of aging, as the accumulation of the unnatural D-form seems to imply little or no turnover of the myelin-rich white matter where it is found to occur. We will seek to relate D-aspartate accumulation rate with altered functions associated with specific brain regions, with such age- or myelin-related pathologies as senile dementia, Parkinson's, Alzheimer's and Binswanger's Diseases, and with chemical factors such as drug or alcohol abuse, calcium imbalance or the presence of heavy metals. D-aspartyl residue accummulation rates will be measured in different polypeptide species through isolation of purified myelin protein fractions, and the rate of accumulation will be related to protein carboxymethyl-transferase activity differences between normal and pathological brains. A cooperative arrangement between the Universities of Miami and California (Los Angeles and Irvine), will bring the skills of chemists, biochemists, neurophysiologists and pathologists to bear on the problem, with the ultimate goal of seeking intervention mechanisms for age-related brain pathology or dysfunction related to racemization.

这个程序的目的是确定神经生理，生化， D-天冬氨酸蓄积的病理和解剖学意义 随着年龄的增长，人脑中的蛋白质出现白色物质，这是最近出现的一种现象 在这个实验室里发现的。 D-天冬氨酸的稳定积累， 推测是由普通L-酸的外消旋化引起的，可能与 疾病和衰老的功能障碍，作为非自然的积累， D型似乎意味着富含髓鞘的白色物质很少或没有周转 在发现发生的地方。 我们将试图把D-天冬氨酸 与特定脑功能相关的功能改变的蓄积率 区域，与年龄或髓鞘相关的病理，如老年性痴呆， 帕金森氏症，阿尔茨海默氏症和宾斯万格氏症，以及化学 因素，如药物或酒精滥用，钙不平衡或存在 重金属 D-乙酰基残留物的模拟率将在 通过分离纯化的髓磷脂蛋白的不同多肽种类 分数，和积累的速度将与蛋白质 羧甲基转移酶活性差异正常和 病态的大脑 大学之间的合作安排， 迈阿密和加州（洛杉矶和欧文），将带来的技能， 化学家、生物化学家、神经生理学家和病理学家， 问题，最终目标是寻求干预机制， 年龄相关的脑病理或与外消旋化相关的功能障碍。