Intranasal TIDM peptide for tauopathy

用于治疗 tau 蛋白病的鼻内 TIDM 肽

• 批准号: 10059127
• 负责人: KALIPADA PAHAN
• 金额: $ 39.25万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059127
• 关键词: Alzheimer' s Disease; Applications Grants; Bacteria; Binding; Brain; Brain Injuries; Cells; Development; Engineering; Flagellin; Frontotemporal Dementia; Inflammation; Innate Immune System; Intranasal Administration; Link; Microglia; Monitor; Mus; Mutate; Natural Immunity; Neurodegenerative Disorders; Neurofibrillary Tangles; Outcome; Pathologic; Pathology; Pathway interactions; Peptides; Progressive Supranuclear Palsy; Specificity; TLR2 gene; Tauopathies; Testing; Therapeutic; Toll-like receptors; Transgenic Mice; Viral; Virus; adaptive immunity; brain parenchyma; cell type; effective therapy; familial Alzheimer disease; hyperphosphorylated tau; inhibitor/antagonist; neuroinflammation; novel; prospective; tau Proteins; tau aggregation; tau-1

Effective reduction of aggregated tau from the brain parenchyma is expected to reduce the development and progression of both sporadic and familial AD, progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), and other tauopathies. However, pathways for lowering aggregated tau from the brain are poorly understood. Neuroinflammation is another hallmark of neurodegenerative disorders and recently it has been shown that the progression of phospho-tau pathology is driven by microglia and that microglial activation forms the crucial link between tau aggregation and brain damage. Here, we want to test a novel hypothesis that intranasal administration of wild type TLR2-interacting domain of MyD88 (wtTIDM) peptide suppresses microglial inflammation (Specific aim I) and decreases tauopathy (Specific aim II) in P301S transgenic mice via TLR2. A positive outcome of this cutting-edge R21 grant proposal will delineate a new crosstalk between TLR2 and tauopathy and describe if selective targeting of activated status of TLR2 by wtTIDM peptide reduces tangle pathology, highlighting the discovery of a prospective intranasal agent to reduce tau pathology in AD, PSP, FTD, and other tauopathies. 1

有效减少脑实质聚集的tau蛋白有望减少发育和