NEURONOTROPHIC FACTORS IN AGING AND ALZHEIMER'S DISEASE

我们提出的实验包括体内和体外研究 神经生长因子和成纤维细胞生长因子的合成及其作用 蛋白质产物的mRNA杂交或免疫细胞化学，在 这些因素中的每一个都是在大脑的哪个区域合成的，是否有 是衰老过程中的变化。体外研究将包括 开发生产可用数量的生长因子和 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 因子可以使神经元在老化过程中免于退化。虽然 直到最近，神经营养因子才被描述为重要的 对于成年大脑中的神经元存活，它们似乎是有希望的 研究人类衰老的机制。一种或多种可能性 进化成治疗剂的因素已经被提出。虽然为时过早 应该避免人体实验，最初的实验是有用的 关于这些生物机制在人类中的相关性的信息 老龄化，指导基础科学工作。在后方，我们还将研究 从人类受试者L脑组织中获得的这些生长因子 包括青年和老年受试者，以及阿尔茨海默病患者。 我们实验室联合输注NGF取得了良好的效果。 将肾上腺髓质组织移植到基底节。 一位帕金森氏症患者。因为这种NGF注射并没有伤害到 可能对患者有有益的影响，我们建议试行 探讨神经生长因子对阿尔茨海默病患者的影响。

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.