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.

基底前脑内含有受体的胆碱能神经元 神经生长因子。 多个融合的证据有 证明基底前脑神经元在 阿尔茨海默氏病。 导致皮质中的胆碱能赤字发生 在疾病过程的早期，高度与严重程度和高度相关 阿尔茨海默氏病的持续时间。 这导致了以下假设 神经生长因子的营养支持受损会导致退化 在这个重要地区可见。 迄今为止，还没有直接证据 支持这一论点，尽管我们认为这个假设有 对研究的调查很差，相反的结果是基于有限的 并可能误解数据。 我们最近观察到 与皮质和皮质相比 基底核内神经元的杏仁核突出神经元在 阿尔茨海默氏病。 我们认为这些神经元的保存可能 由于海马包含三倍的神经 生长因素，如果确实正在救出神经生长因子，则应退化 该疾病中的胆碱能神经元。 此外，之间的相关性 将进行基础前脑变性（胆碱能和非胆碱能力） 在早期诊断的阿尔茨海默氏病病例中具有皮质病理学 验尸。 最后，神经生长因子的状态 阿尔茨海默氏病中的受体将通过定量评估 免疫摄影程序。 这些数据将确定是否在那里 是每个基础前脑神经元的神经生长因子受体的减少 因此，在阿尔茨海默氏病中，这些细胞内会导致变性。 另外，没有变化或受体上调表明 这些神经元将能够响应神经生长因子 治疗。