Dietary glycomacropeptide (GMP) for neuroprotection and cognitive enhancement

描述（由申请人提供）：阿尔茨海默病的特征是β -淀粉样蛋白（Abeta）在大脑中聚集，广泛的神经变性和认知能力下降。我们的工作重点是通过改变脑神经节苷脂分布来改善阿尔茨海默病的病理和改善记忆。我们已经证明，在动物模型中，操纵脑神经节苷脂具有神经保护作用，可以减少淀粉样蛋白聚集，并改善行为。尽管操作方法不同，但它们都有一个共同点，即能够增加大脑中GM1的水平。GM1已被证明在许多不同的制剂中具有神经保护和增强认知的作用。一份发表的关于野生型仔猪的报告表明，饲粮中添加糖大肽（GMP）可以改善空间记忆，并增加大脑中唾液化神经节苷的水平。尽管该研究没有报告特定神经节苷脂的水平，但认知能力的增强表明GM1升高。我们的目标是了解神经节苷类在阿尔茨海默病中的作用，以及它们与记忆障碍（阿尔茨海默病最早的认知症状）之间的关系。本应用的目的是确定在5xFAD转基因小鼠模型中，膳食给药GMP是否能成功缓解阿尔茨海默病的特征。本研究的一般假设是，5个月的GMP管理可以成功地减少斑块形成，防止成年突变小鼠的神经变性和记忆障碍。在本实验中，将对5xFAD和野生型小鼠分别饲喂GMP日粮或对照分离大豆蛋白日粮。将评估空间记忆，以及焦虑和感觉运动功能的对照测试。死后分析将评估阿尔茨海默病相关的神经病理学和细胞死亡，以及脂质生物化学。成功减少转基因小鼠的淀粉样蛋白负担、细胞死亡和记忆障碍，可能为阿尔茨海默病的新治疗策略提供见解，这些治疗方法可以减少或预防阿尔茨海默病患者的痴呆症。

DESCRIPTION (provided by applicant): Alzheimer's disease is characterized by the aggregation of beta-amyloid (Abeta) protein in the brain, widespread neurodegeneration, and cognitive decline. Our work focuses on amelioration of Alzheimer's pathology and improving memory by modifying brain ganglioside distribution. We have shown that manipulating brain gangliosides in vivo are neuroprotective and reduce amyloid aggregation, and improve behavior in animal models. Although the manipulations differ, they all have in common the ability to increase the levels of GM1 in the brain. GM1 has been shown to be neuroprotective and enhance cognition in many different preparations. A published report with wild-type piglets demonstrates that dietary glycomacropeptide (GMP) improves spatial memory and increases levels of sialylated gangliosides in the brain. Although the study did not report levels of specifi gangliosides, the enhanced cognition suggests that GM1 is elevated. Our goal is to understand the role of gangliosides in Alzheimer's disease and how they relate to memory impairment, the earliest cognitive symptom of the disease. The objective of this application is to determine whether dietary administration of GMP is successful in alleviating features of Alzheimer's disease in the 5xFAD transgenic mouse model. The general hypothesis of the proposed research is that 5 months' administration of GMP will successfully reduce plaque formation and prevent neurodegeneration and memory impairments in adult mutant mice. In the proposed experiments, a GMP diet or control isolated soy protein (ISP) diet will be administered to 5xFAD and wild-type control mice. Spatial memory will be assessed, as well as control tests for anxiety and sensorimotor function. Post-mortem analyses will assess Alzheimer-related neuropathology and cell death, as well as lipid biochemistry. Successfully reducing amyloid burden, cell death, and memory impairment in the transgenic mice may provide insight into new treatment strategies for Alzheimer's disease-- treatments that could reduce or prevent dementia in Alzheimer patients.