NGF TROPISM IN ALZHEIMER'S DISEASE

阿尔茨海默病中的 NGF 趋向性

• 批准号: 3790430
• 负责人: JEFFREY H KORDOWER
• 金额: --
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 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/3790430
• 关键词: Alzheimer's disease; GABA receptor; Huntington's disease; Parkinson's disease; amygdala; autoradiography; biological signal transduction; brain; brain mapping; cholinergic receptors; dementia; flavins; glutamate decarboxylase; growth factor receptors; hippocampus; human tissue; immunocytochemistry; motor cortex; nervous system disorder; neural degeneration; neurons; neurotrophic factors; postmortem; prosencephalon; receptor binding; receptor expression

Cholinergic neurons within the basal forebrain containing receptors for nerve growth factor. Multiple converging lines of evidence have demonstrated that basal forebrain neurons consistently degenerate in Alzheimer's disease. The resulting cholinergic deficit in cortex occurs early in the disease process and highly correlates with the severity and duration of Alzheimer's disease. This has led to the hypothesis that impaired trophic support by nerve growth factor leads to the degeneration seen in this important region. To date, there is no direct evidence to support this contention although we have argued that this hypothesis had been poorly investigated and results to the contrary are based upon limited and potentially misinterpreted data. We have recently observed that the cholinergic septohippocampal system, in contrast to the cortical and amygdaloid projecting neurons within the nucleus basalis,is not impaired in Alzheimer's disease. We contend that the preservation of these neurons may be due to the fact that the hippocampus contains three times as much nerve growth factor, should degenerate if nerve growth factor is indeed rescuing the cholinergic neurons in this disease. Furthermore, correlations between basal forebrain degeneration (cholinergic and noncholinergic) will be made with cortical pathology in early diagnosed cases of Alzheimer's disease which have come to post-mortem. Finally, the status of nerve growth factor receptors in Alzheimer's disease will be assessed via a quantitative immunoautoradiographic procedure. These data will determine whether there is a reduction of nerve growth factor receptors per basal forebrain neuron in Alzheimer's disease thus precipitating degeneration within these cells. Alternatively, no change or receptor up-regulation would indicate that these neurons would be capable of responding to nerve growth factor therapy.

基底前脑内的胆碱能神经元含有受体 神经生长因子。 多条汇聚的证据表明 证明基底前脑神经元在 阿尔茨海默病。 由此产生的皮质胆碱能缺陷发生 发生在疾病过程的早期，与疾病的严重程度和程度高度相关 阿尔茨海默病的持续时间。 这导致了这样的假设： 神经生长因子的营养支持受损导致退化 在这个重要的地区看到了。 迄今为止，还没有直接证据表明 支持这个论点，尽管我们认为这个假设已经 未经充分调查，相反的结果是基于有限的 以及可能被误解的数据。 我们最近观察到 胆碱能隔海马系统，与皮质和 基底核内的杏仁核投射神经元在 阿尔茨海默病。 我们认为这些神经元的保存可能 因为海马体含有三倍的神经 生长因子，如果神经生长因子确实有拯救作用的话，应该会退化 这种疾病中的胆碱能神经元。 此外，之间的相关性 基底前脑变性（胆碱能和非胆碱能） 阿尔茨海默病早期诊断病例中的皮质病理学 已进行尸检。 最后，神经生长因子的现状 阿尔茨海默氏病的受体将通过定量评估 免疫放射自显影程序。 这些数据将决定是否存在 每个基底前脑神经元的神经生长因子受体减少 在阿尔茨海默病中，从而加速这些细胞内的退化。 或者，没有变化或受体上调表明 这些神经元能够对神经生长因子做出反应 治疗。