天冬酰胺内肽酶剪切Synapsin介导阿尔茨海默病突触功能障碍的研究

阿尔茨海默病（AD）是临床上最常见的神经变性疾病，也是导致痴呆最常见的原因。目前的研究认为突触功能异常是AD的重要病理变化，也是导致认知功能障碍的重要病理学基础，但AD患者脑内突触功能异常的分子机制尚未阐明。Synapsin是调节突触功能的重要蛋白，主要分布在突触前膜，调节突触囊泡的转运、神经递质的释放和重回收。我们前期的研究发现天冬酰胺内肽酶（AEP）能够剪切Synapsin，但AEP剪切Synapsin对突触功能影响的分子机制及其在AD发病中的作用并不清楚。本研究中，我们将使用AEP基因敲除小鼠及AD转基因小鼠，联合运用动物行为学、组织形态学、细胞生物学和分子生物学等方法，深入探讨AEP剪切Synapsin的分子机制，明确AEP剪切Synapsin对突触功能的影响及其在AD发病中的作用，以期明确AD脑内突触功能障碍的机制，并为AD的防治提供新的靶点。

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and the most common cause of dementia. Current research suggests that synaptic dysfunction is an important pathological change in AD, and the pathological basis of cognitive dysfunction. However, the molecular mechanisms underlying synaptic dysfunction in AD remain elusive. Synapsin plays a key role in regulating synapse function. It mainly distributes in the presynaptic membrane, which modulates synaptic vesicles transportation, neurotransmitter release and recovery. Our previous study indicated that a novel protease asparagine endopeptidase (AEP) cleaves synapsin and interferes with its normal functions. However, the molecular mechanisms involved in the cleavage of synapsin and the role of synapsin in the pathogenesis of AD is poorly understood. In this study, we will use AEP knockout mice and transgenic AD mouse models, in combination with mouse behavior, histology, cell biology and molecular biology to demonstrate the molecular mechanisms of AEP-mediated synapsin cleavage in AD. We anticipated to verifying the role of AEP in synaptic dysfunction in AD, and providing novel target for treating AD.