Exercise Mimetics for Dementia and Alzheimer's Disease

项目摘要 痴呆症或重大神经认知障碍是一种认知能力显著下降的状况，它会损害 独立生活。学习和记忆、执行功能、知觉-运动功能、社会认知和 语言可能会受到影响。尽管痴呆症通常与衰老有关，但它不是一种自然因素 衰老过程的影响。痴呆症与多种疾病有关，但最常见的与阿尔茨海默病有关 (60%-80%)。AD是一种进行性神经退行性疾病，其临床特征包括记忆丧失， 认知障碍和痴呆症。目前有500多万美国人患有AD，预计 到2050年增加到1600万。目前，美国65岁以上的人中有10% 得了AD。目前治疗阿尔茨海默病的方法疗效有限，亟需改进 药物疗法。AD的特点是形成老年斑和神经原纤维缠结。 受影响个体的灰质。老年斑是由细胞外沉积的 不溶性淀粉样β蛋白(Aβ)多肽，通常与丰富的小胶质细胞(大脑驻留)有关 巨噬细胞)和星形胶质细胞。ERRs是在氧化调节中起关键作用的孤儿受体 新陈代谢，我们发现它们作为运动模拟物发挥作用，并增强认知功能 并能减少AD动物模型中淀粉样斑块的形成。这个项目的目标是 开发优化的ERR激动剂，可能成为治疗痴呆症和阿尔茨海默病的有效药物 疾病。

Project Summary Dementia or major neurocognitive disorder is a condition of significant cognitive decline that impairs independent living. Learning and memory, executive function, perceptual-motor function, social cognition, and language may be affected. Although dementia is typically associated with aging, it is not a natural component of the aging process. Dementia is associated with several diseases, but most commonly associated with AD (60-80%). AD is a progressive neurodegenerative disease with clinical features that include memory loss, cognitive impairment and dementia. More than 5 million Americans currently live with AD and it is expected to increase to as much as 16 million by 2050. Ten percent of individuals over the age of 65 in the U.S. currently have AD. Current treatments for AD have limited efficacy and there is a significant need for improved pharmacological therapies. AD is characterized by the formation of senile plaques and neurofibrillary tangles in the grey matter of affected individuals. The senile plaques are composed of extracellular deposition of insoluble amyloid beta (Aβ) peptides that are typically associated with a wealth of microglia (brain resident macrophages) and astrocytes. ERRs are orphan receptors that play a key role in regulation of oxidative metabolism, and we have discovered that they function as exercise mimetics and enhance cognitive function in normal and aged mice as well as decrease amyloid plaques in animal models of AD. The goal of this project is to develop optimized ERR agonists that may be effective agents in treatment of dementia and Alzheimer's disease.