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。我们的工作重点是改善阿尔茨海默病的病理和改善记忆通过修改脑神经节苷脂分布。我们已经证明，在体内操作脑神经节苷脂具有神经保护作用，减少淀粉样蛋白聚集，并改善动物模型的行为。虽然操作方法不同，但它们都具有增加大脑中GM 1水平的能力。GM 1在许多不同的制剂中已被证明具有神经保护作用并增强认知。一份关于野生型仔猪的已发表报告表明，饮食中的糖巨肽（GMP）可改善空间记忆，并增加大脑中唾液酸化神经节苷脂的水平。虽然该研究没有报告特定神经节苷脂的水平，但增强的认知表明GM 1升高。我们的目标是了解神经节苷脂在阿尔茨海默病中的作用，以及它们与记忆障碍（该疾病最早的认知症状）的关系。本申请的目的是确定GMP的饮食施用是否成功地减轻5xFAD转基因小鼠模型中阿尔茨海默病的特征。拟议研究的一般假设是，5个月的GMP管理将成功地减少斑块形成，并防止成年突变小鼠的神经退行性变和记忆障碍。在拟定的实验中，将GMP饲料或对照分离大豆蛋白（ISP）饲料给予5xFAD和野生型对照小鼠。将评估空间记忆，以及焦虑和感觉运动功能的控制测试。尸检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。成功地减少转基因小鼠中的淀粉样蛋白负荷、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--这些治疗可以减少或预防阿尔茨海默病患者的痴呆症。 公共卫生相关性：拟议的实验将测试食品添加剂糖巨肽（GMP）对记忆和阿尔茨海默病相关神经病理学的影响。GMP的使用不仅代表了一种新的治疗策略，也代表了阿尔茨海默病的一种新的治疗靶点。这些实验与国家老龄化研究所和国家神经疾病和中风研究所的既定目标一致。

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. PUBLIC HEALTH RELEVANCE: The proposed experiments will test the effects of the food additive glycomacropeptide (GMP) on memory and Alzheimer-related neuropathology. The use of GMP represents not only a novel treatment strategy, but a novel therapeutic target for Alzheimer's disease. These experiments are consistent with the stated goals of National Institute on Aging and National Institute of Neurological Disorders and Stroke.