Exercise Mimetics for Dementia and Alzheimer's Disease

治疗痴呆和阿尔茨海默病的模拟运动

• 批准号: 10586188
• 负责人: Thomas P Burris
• 金额: $ 226.29万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586188
• 关键词: Address; Adult; Affect; Aging; Agonist; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; American; Amyloid beta-Protein; Animal Model; Applications Grants; Astrocytes; Biochemical; Brain; Cell Line; Cell Respiration; Cells; Chemicals; Clinical; Cognition; Cytoskeletal Proteins; Data; Dementia; Deposition; Development; Disease; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Estrogens; Exercise; Genetic Transcription; Goals; Hippocampus; Impaired cognition; Impairment; Independent Living; Individual; Knockout Mice; Language; Learning; Ligand Binding; Ligands; Macrophage; Memory; Memory Loss; Metabolic; Metabolism; Microglia; Modeling; Motor; Mus; Names; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Nuclear Orphan Receptor; Nuclear Receptors; Orphan; Oxidative Regulation; Peripheral; Pharmaceutical Chemistry; Play; Process; Property; Research; Role; Scheme; Senile Plaques; Skeletal Muscle; Tissues; abeta deposition; aged; amyloid precursor protein processing; clinical candidate; cognitive enhancement; cognitive function; design; drug discovery; estrogen-related receptor; executive function; extracellular; gray matter; human old age (65+); hyperphosphorylated tau; improved; mimetics; mouse model; neurocognitive disorder; neurogenesis; novel therapeutics; pharmacologic; receptor; research clinical testing; social cognition; tool; xenoestrogen; Address; Adult; Affect; Aging; Agonist; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; American; Amyloid beta-Protein; Animal Model; Applications Grants; Astrocytes; Biochemical; Brain; Cell Line; Cell Respiration; Cells; Chemicals; Clinical; Cognition; Cytoskeletal Proteins; Data; Dementia; Deposition; Development; Disease; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Estrogens; Exercise; Genetic Transcription; Goals; Hippocampus; Impaired cognition; Impairment; Independent Living; Individual; Knockout Mice; Language; Learning; Ligand Binding; Ligands; Macrophage; Memory; Memory Loss; Metabolic; Metabolism; Microglia; Modeling; Motor; Mus; Names; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Nuclear Orphan Receptor; Nuclear Receptors; Orphan; Oxidative Regulation; Peripheral; Pharmaceutical Chemistry; Play; Process; Property; Research; Role; Scheme; Senile Plaques; Skeletal Muscle; Tissues; abeta deposition; aged; amyloid precursor protein processing; clinical candidate; cognitive enhancement; cognitive function; design; drug discovery; estrogen-related receptor; executive function; extracellular; gray matter; human old age (65+); hyperphosphorylated tau; improved; mimetics; mouse model; neurocognitive disorder; neurogenesis; novel therapeutics; pharmacologic; receptor; research clinical testing; social cognition; tool; xenoestrogen

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.

项目摘要 痴呆症或主要神经认知障碍是严重认知下降的疾病，会损害 独立生活。学习和记忆，执行功能，感知运动功能，社会认知和 语言可能会受到影响。尽管痴呆通常与衰老有关，但它不是天然成分 衰老过程。痴呆与几种疾病有关，但最常见于AD （60-80％）。 AD是一种进行性神经退行性疾病，具有临床特征，包括记忆丧失， 认知障碍和痴呆症。目前有超过500万美国人居住在广告中，预计将 到2050年增加到多达1600万。目前，美国65岁以上的个人中有百分之十 有广告。当前的AD治疗效率有限，需要改善 药理疗法。 AD的特征是形成老年斑块和神经原纤维缠结 受影响个人的灰质。老年斑块由细胞外沉积组成 不溶性淀粉样β（Aβ）肽，通常与大型小胶质细胞（脑居民）相关 巨噬细胞）和星形胶质细胞。错误是孤儿受体，在调节氧化中起关键作用 代谢，我们发现它们充当运动模仿物并增强认知功能 正常小鼠和老化的小鼠以及AD动物模型中的淀粉样斑块减少。这个项目的目标是 开发优化的ERR激动剂，这些激动剂可能是治疗痴呆和阿尔茨海默氏症的有效药物 疾病。