Targeting inflammatory mechanisms in Alzheimer's disease.

针对阿尔茨海默病的炎症机制。

• 批准号: nhmrc : 300467
• 负责人: A/Pr Mark Raftery
• 金额: $ 26.19万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/targeting-inflammatory-mechanisms-alzheimers-disease/77957
• 关键词: Targeting; inflammatory; mechanisms; Alzheimer; disease.

Alzheimer s disease accounts for the majority of dementia cases and is the most common cause for nursing home requirements in Australia. It is not a disease that is confined to old age as it can also affect individuals in their 20s and 30s. There is currently no cure for Alzheimer's disease, largely because the underlying cause is unknown. Deposition of the amyloid-beta protein within the brain of Alzheimer's disease patients is thought to be responsible for the neuronal cell loss which underlies the dementia. However, amyloid-beta protein deposition can occur in the absence of dementia and in the asbence of significant neuronal cell loss, suggesting that an alternative mechanism of neurotoxicity exists. Inflammation is a consistent feature of the Alzheimer's disease brain. We have preliminary evidence to suggest that inflammation is responsible for the neurotoxicity in Alzheimer's disease. We have recently observed a significant inflammatory response surrounding an unidentified protein in the brains of individuals with a familial form of Alzheimer's disease due to a genetic mutation. This inflammatory response is not associated with the significant amyloid-beta protein deposition seen in these cases suggesting that a novel potent inflammatory stimulus exists. Furthermore, these cases have greater neuronal cell loss and a shorter disease duration, both indicators of increased neurotoxicity. The present study is designed to determine the toxicity of inflammation and the stimulus driving this response in the Alzheimer's disease brain using tools for protein and gene analysis, as well as determining the extent of inflammation-mediated toxicity on neuronal cells grown in culture. Only by addressing these aims can we concentrate on developing safe and effective therapeutic strategies to prevent or treat the disease process.

老年痴呆症占痴呆症病例的大多数，是澳大利亚养老院要求的最常见原因。它不是一种仅限于老年的疾病，因为它也可以影响20多岁和30多岁的人。目前还没有治愈阿尔茨海默病的方法，主要是因为根本原因尚不清楚。淀粉样β蛋白在阿尔茨海默病患者脑内的沉积被认为是导致神经元细胞损失的原因，而神经元细胞损失是痴呆的基础。然而，淀粉样β蛋白沉积可发生在没有痴呆和显著神经元细胞损失的情况下，这表明存在神经毒性的替代机制。炎症是阿尔茨海默病大脑的一贯特征。我们有初步的证据表明，炎症是负责阿尔茨海默氏症的神经毒性。我们最近观察到一个显着的炎症反应周围的一个未知的蛋白质在个人的大脑中与一个家族形式的阿尔茨海默氏病由于基因突变。这种炎症反应与这些病例中观察到的显著淀粉样β蛋白沉积无关，表明存在新的强效炎症刺激。此外，这些病例的神经元细胞损失更大，疾病持续时间更短，这两个指标都表明神经毒性增加。本研究旨在确定炎症的毒性和使用蛋白质和基因分析工具驱动阿尔茨海默病大脑中这种反应的刺激，以及确定炎症介导的对培养中生长的神经元细胞的毒性程度。只有实现这些目标，我们才能集中精力开发安全有效的治疗策略，以预防或治疗疾病过程。