NEURONOTROPHIC FACTORS IN AGING AND ALZHEIMER'S DISEASE

衰老和阿尔茨海默病中的神经营养因子

• 批准号: 3802443
• 负责人: LARS OLSON
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802443
• 关键词: Alzheimer's disease; acetylcholine; aging; brain; central nervous system; cerebral ventricles; dementia; fibroblast growth factor; genetic recombination; growth factor receptors; high performance liquid chromatography; hippocampus; human subject; immunocytochemistry; in situ hybridization; laboratory rat; messenger RNA; nervous system transplantation; neural growth associated protein; neurons; neuropeptides; neuropharmacology; neurotrophic factors; polymerase chain reaction; postmortem; protein biosynthesis; protein sequence; tissue /cell culture; transfection

Our proposed experiments encompass in vivo and in vitro studies of the synthesis and actions of neuronotrophic factors in the NGF and FGF hybridization of mRNA or immunocytochemistry of the protein product, in which brain region each of these factors is synthesized ad whether there are changes during senescence. The in vitro studies will include the development of systems to produce useable amounts of growth factors and which can also be transplanted into the brain. We will used such transplants, as well as other means of administration, to determine if the factors can rescue neurons from degeneration during aging. Although neuronotrophic factors have only recently been characterized as important for neuron survival in the adult brain, they would seem to be promising mechanisms for the study of aging in humans. The possibility of one or more factors evolving into therapeutic agents has been raised. While premature human experimentation should be avoided, it would be useful to have initial information about the relevance of these biological mechanisms in human aging, to guide the basic science work. In the rear, we will also study these growth factors in brain tissue obtained from human subjects,l including young and aged subjects, and patients with Alzheimer's Disease. Our laboratory has obtain favorable results with infusion of NGF, together with transplantation of adrenal medullary tissue, into the basal ganglia of a patient with Parkinsons's disease. Because this NGF infusion did not harm the patient and may have had a beneficial effect, we propose a pilot exploration of the effects of NGF in patients with Alzheimer's disease.

我们提出的实验包括在体内和体外的研究， 神经营养因子在神经生长因子和成纤维细胞生长因子中的合成和作用 mRNA的杂交或蛋白产物的免疫细胞化学， 这些因素中的每一个都是由哪个大脑区域合成的， 是衰老过程中的变化体外研究将包括 开发系统以生产可用数量的生长因子， 也可以移植到大脑中。我们将使用这样的 移植，以及其他管理手段，以确定是否 因子可以挽救神经元免于老化过程中的退化。虽然 神经营养因子直到最近才被描述为重要的 对于成年人大脑中的神经元存活来说， 研究人类衰老的机制。一个或多个的可能性 已经提出了演变成治疗剂的因素。虽然过早 应避免人体试验，因此， 关于这些生物学机制在人类中的相关性的信息 指导基础科学工作。在后方，我们也将研究 从人类受试者获得的脑组织中的这些生长因子， 包括年轻和老年受试者以及阿尔茨海默病患者。 本实验室通过输注神经生长因子， 移植肾上腺髓质组织，进入基底神经节， 帕金森氏症患者因为这种NGF输注没有伤害 病人，并可能有一个有益的影响，我们建议试点 探讨神经生长因子在阿尔茨海默病患者中的作用。