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GERIATRIC DEMENTIA RESEARCH CLINIC

GERIATRIC DEMENTIA RESEARCH CLINIC
老年痴呆症研究诊所
批准号:
3090714
负责人:
JOHN P BLASS
金额:
$34.65万
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-06-01 至 1987-05-31
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项目摘要

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中文摘要
翻译
老年痴呆症研究诊所将专注于神经代谢方面 老年痴呆症。 葡萄糖氧化和 神经递质代谢在痴呆症患者的大脑中会减少, 受试者体内。 该项目是一个综合性的群体, 旨在阐明这些分子基础的研究 异常,并测试它们在改善诊断方面的价值,以及 其潜在的病理生理和治疗意义。 痴呆症评估中仔细诊断的患者和对照组 临床和另一个尸检系列将进行研究。 新的信号分析 133氙洗脱曲线和推定的胆碱能和其他 将开发血液和脑脊液中的神经递质标记物 帮助诊断。 本单元和两个单元最近的观察结果 英国的实验室已经证明了阿尔茨海默氏症的内在异常 葡萄糖利用的两个关键酶--磷酸果糖激酶 (PFK)和丙酮酸脱氢酶(PDHC)。 科索沃爱国阵线、科索沃民主人权委员会和其他组织的活动 代谢和神经递质标记酶, 将比较尸检阿尔茨海默病和对照大脑的区域; PFK将 也可以在非神经组织中表征,因为最近的数据表明, 这种异常在阿尔茨海默病成纤维细胞中持续存在。 在 此外,还对PFK和PDHC的活性及PFK同工酶谱进行了研究。 在临床患者的血细胞和成纤维细胞中研究。 这些 酶将从尸体解剖的组织中纯化并进行动力学研究, 从解剖学上检测结构异常。 铝,a 阿尔茨海默病的假定神经毒素,将检查其影响 对兔脑葡萄糖代谢的影响。 选择性的脆弱性 某些神经元受损葡萄糖catalysts将探讨与大鼠 体外视网膜作为模型系统。 其他调查将研究 治疗剂、营养作用以及可能的关系 免疫功能的改变和内在酶异常之间的关系 老年痴呆淋巴细胞。 这个关于阿尔茨海默氏症的神经化学的项目 疾病的目的还在于鉴定其有用的生物化学标记物或用于治疗疾病的生物化学标记物。 倾向于它。
英文摘要
The Geriatric Dementia Research Clinic will focus on neurometabolic aspects of Alzheimer disease in the elderly. Glucose oxidation and neurotransmitter metabolism are known to decrease in the brains of demented subjects in vivo. This program project is an integrated group of investigations designed to elucidate the molecular bases of these abnormalities and to test their value in improving diagnoses, as well as their potential pathophysiologic and therapeutic significance. Meticulously diagnosed patients and controls from a Dementia Evaluation Clinic and another autopsy series will be studied. New signal analyses of 133Xenon washout curves and measurements of putative cholinergic and other neurotransmitter markers in blood and cerebrospinal fluid will be developed as aids to diagnosis. Recent observations in this unit and in two laboratories in England have demonstrated intrinsic abnormalities Alzheimer brainin two key enzymes of glucose utilization in--phosphofructokinase (PFK) and pyruvate dehydrogenase (PDHC). Activities of PFK, PDHC and other metabolic and neurotransmitter marker enzymes from physiologically relevant regions of autopsy Alzheimer and control brains will be compared; PFK will also be characterized in non-neural tissues, since recent data indicate that the abnormalities in it persist in Alzheimer fibroblasts. In addition, activities of PFK and PDHC and isozyme patterns of PFK will be studied in blood cells and fibroblasts from the clinic patients. These enzymes will be purified from autopsied tissues and studied kinetically and electrophoretically to test for structural abnormalities. Aluminum, a putative neurotoxin in Alzheimer disease, will be examined for its effects on glucose metabolism in rabbit brain. The selective vulnerability of certain neurones to impaired glucose catabolism will be explored with rat retina in vitro as a model system. Other investigations will study therapeutic agents, nutritional effects, and a possible relationship between altered immune function and intrinsic enzymatic abnormalities of Alzheimer lymphocytes. This program on the neurochemistry of Alzheimer's disease also aims to identify useful biochemical marker(s) for it or for a predisposition to it.
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Effects of CAG/Qn Expansions on KGDHC and Other Enzymes
OXIDATIVE/ENERGY METAB IN NEURODEGENERATIVE DISORDERS
  • 批准号:
    2739667
  • 项目类别:
  • 资助金额:
    $3.19万
  • 财政年份:
    1999
  • 负责人:
    JOHN P BLASS
  • 依托单位:
MITOCHONDRIAL DYSFUNCTION IN NEURODENEGENERATION/AGING
MITOCHONDRIAL DYSFUNCTION IN NEURODENEGENERATION/AGING
海外基金