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

轴突转运是几种神经退行性疾病的共同病因，如亨廷顿氏病、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的特征是神经变性、细胞内神经原纤维缠结和主要由淀粉样蛋白前体蛋白（APP）衍生的β淀粉样肽组成的细胞外斑块。最近的证据表明，APP介导轴突运输，因为APP作为运动蛋白激酶- 1的膜受体的功能被假设。我们想要确定app样蛋白APLP1和APLP2是否也介导转运并与运动蛋白复合物的组分相互作用，它们被认为具有类似的功能。某些蛋白质似乎在APP指定的囊泡中沿着轴突特异性运输，这表明关于APP家族成员的假设重叠功能，APLP1和APLP2介导另一类囊泡的运输，这些囊泡含有相同但又独特的货物蛋白。鉴定这些货物蛋白是我们的主要目标。这些分析将有助于阐明app家族成员在AD生理条件和病理中的功能。

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.