Functional analysis of axonal transport vesicles containing APP, APLP1 or APLP2

含有 APP、APLP1 或 APLP2 的轴突转运囊泡的功能分析

• 批准号: 5385113
• 负责人: Professor Dr. Stefan Kins
• 金额: --
• 依托单位: Netzwerk AlternsfoRschung (NAR)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5385113?language=en
• 关键词: Functional; analysis; axonal; transport; vesicles

Axonal transport emerge to represent a common feature in the etiology of several neurodegenerative diseases, such as Huntington's disease, Parkinson's disease, frontotemporal dementia, Creutzfeldt-Jacob disease and Alzheimer's disease (AD). Pathologically, AD is characterized by neurodegeneration, intracellular neurofibrillary tangles and extracellular plaques composed mainly of the beta Amyloid peptide, derived from the amyloid precurser protein (APP). Recent evidence suggests that APP mediates axonal transport, since a function for APP as membrane receptors of the motor protein kinesin-I was postulated. We want to determine if the APP-like proteins APLP1 and APLP2, which are expected to have a similar function, also mediate transport and interact with components of the kinesin motor protein complex. Certain proteins seem to be transported along the axon specifically in those vesicles designated by APP, suggesting in regard to the postulated ovelapping functions of the APP-family members, that APLP1 and APLP2 mediate the transport of another class of vesicles containing identical but also unique cargo proteins. The identification of these cargo proteins is our major goal. These analyses will help to clarify the function of APP-family members under physiological conditions and in the pathology of AD.

轴突运输是几种神经退行性疾病的共同特征，如亨廷顿病、帕金森病、额颞叶痴呆、克雅氏病和阿尔茨海默病（AD）。在病理学上，AD的特征在于神经变性、细胞内神经纤维缠结和主要由β淀粉样肽组成的细胞外斑块，β淀粉样肽来源于淀粉样蛋白（APP）。最近的证据表明，APP介导轴突运输，因为APP作为运动蛋白驱动蛋白-I的膜受体的功能被假定。我们想确定APP样蛋白APLP 1和APLP 2，预计具有类似的功能，也介导运输和相互作用的驱动蛋白马达蛋白复合物的组件。某些蛋白质似乎沿着轴突运输，特别是在APP指定的囊泡中，这表明关于APP家族成员的假定卵定位功能，APLP 1和APLP 2介导含有相同但也是独特的货物蛋白的另一类囊泡的运输。这些货物蛋白的鉴定是我们的主要目标。这些分析将有助于阐明APP家族成员在生理条件下和AD病理学中的功能。