STUDY OF D-ASPARTATE ACCUMULATION IN AGING BRAIN

这个程序被设计来确定神经生理，生化， D-天冬氨酸蓄积的病理学和解剖学意义 随着年龄的增长，人脑白质中的蛋白质最近出现了一种现象 在这个实验室里发现的。D-天冬氨酸的稳定积累， 推测是由于常见的L酸的外消旋所致，可能与 以疾病和衰老功能障碍为积聚的非自然因素 D型似乎意味着富含髓鞘的白质很少或根本没有周转。 在发现它发生的地方。我们将寻求将D-天冬氨酸 与特定大脑相关的功能改变的蓄积率 患有老年痴呆症等与年龄或髓鞘相关的病理的地区， 帕金森氏症、阿尔茨海默氏症和Binswanger病，以及与化学物质 诸如滥用药物或酒精、钙失衡或存在 重金属。D-天冬氨酸残留量积累率将在 从纯化的髓鞘蛋白中分离不同种类的多肽 组分，而积累的速度将与蛋白质有关 正常人和正常人的羧甲基转移酶活性差异 病态的大脑。两所大学之间的合作安排 迈阿密和加州(洛杉矶和欧文)，将带来 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 与年龄相关的脑部病变或外消旋化相关的功能障碍。

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.