FORCE MICROSCOPY OF ABETA & ALPHA SYNUCLEIN AGGREGATION

ABETA 力显微镜

• 批准号: 2863077
• 负责人: Jason Howard Hafner
• 金额: $ 3.03万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2863077
• 关键词: alpha synuclein; amyloid proteins; atomic force microscopy; bioengineering /biomedical engineering; bioimaging /biomedical imaging; chemical aggregate; electrochemistry; image enhancement; nanotechnology; neurofibrillary tangles; protein structure; technology /technique development

Abnormal protein deposits in the brain which contain fibrilized forms of Abeta and alpha-synuclein proteins are characteristic of Alzheimer's Disease and Parkinson's Disease, and they may play a causative role in neurodegeneration. Detailed knowledge of the aggregation mechanisms of Abeta and alpha-synuclein would elucidate the steps in disease progression, potentially identifying therapeutic strategies. The proposed research will continue a scanning force microscopy (SFM) study of Abeta and initiate similar research on alpha-synuclein. The SFM studies will use recently developed carbon nanotube tips, which allow higher resolution imaging than previously attained. Chemical force microscopy (CFM) with nanotube tips will be used to map the functional group distribution on the protein aggregates with high resolution. Concurrently, the further sharpening of nanotube tips will be pursued by sputtering and electrochemical etching techniques. The ultimate goal, a tip which ends in an individual singe-walled nanotube, should achieve 1 - 2 nm resolution in SFM and CFM, an order of magnitude improvement over standard SFM tips. These ultrahigh resolution tips will be used to achieve a molecular scale understanding of Abeta and alpha-synuclein aggregation.

脑中含有纤维化形式的Abeta和α-突触核蛋白的异常蛋白质沉积是阿尔茨海默病和帕金森病的特征，并且它们可能在神经变性中起致病作用。 Abeta和α-突触核蛋白聚集机制的详细知识将阐明疾病进展的步骤，可能确定治疗策略。 拟议的研究将继续对Abeta进行扫描力显微镜（SFM）研究，并启动对α-突触核蛋白的类似研究。 SFM研究将使用最近开发的碳纳米管尖端，它允许比以前更高的分辨率成像。 具有纳米管尖端的化学力显微镜（CFM）将用于以高分辨率绘制蛋白质聚集体上的官能团分布。同时，将通过溅射和电化学蚀刻技术进一步锐化纳米管尖端。 最终的目标是，一个尖端结束于一个单独的单壁纳米管，应达到1 - 2纳米的分辨率在SFM和CFM，一个数量级的改进超过标准的SFM提示。 这些高分辨率提示将用于实现对Abeta和α-突触核蛋白聚集的分子尺度理解。