Intranasal TIDM peptide for tauopathy

有效地减少脑实质中聚集的tau有望减少发育和 散发性和家族性阿尔茨海默病(AD)、进行性核上性麻痹(PSP)、 额颞性痴呆(FTD)和其他神经官能症。然而，降低聚合tau的途径来自 人们对大脑知之甚少。神经炎是神经退行性疾病的另一个标志， 最近的研究表明，磷酸化tau病理的进展是由小胶质细胞驱动的，并且 小胶质细胞的激活形成了tau聚集和脑损伤之间的关键环节。在这里，我们想测试一下 鼻腔给药MyD88野生型TLR2相互作用结构域的新假说 (WtTIDM)肽抑制P301S转基因小鼠小胶质细胞炎症并减轻张力障碍 通过TLR2。这项拨款提案的积极结果将勾勒出TLR2和TLR2之间的新串扰 并描述wtTIDM多肽选择性靶向TLR2激活状态是否可减少缠结 病理学，强调了一种预期的鼻腔用药的发现，以减少AD，PSP， FTD和其他tauopathy。 行政补充：TLR2存在于大脑中不同类型的细胞中。例如，在大脑中，在 除小胶质细胞外，TLR2也在神经元中表达。因此，在这里，我们将调查一下 神经细胞和小胶质细胞TLR2在肌萎缩侧索硬化症及wtTIDM多肽介导的肌萎缩侧索硬化症清除中的作用 改善P301S转基因小鼠的认知行为。

Effective reduction of aggregated tau from the brain parenchyma is expected to reduce the development and progression of both sporadic and familial Alzheimer’s disease (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 and decreases tauopathy in P301S transgenic mice via TLR2. A positive outcome of this 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. Administrative supplement: TLR2 is present in different cell types in the brain. For example, in the brain, in addition to microglia, TLR2 is also expressed in neurons. Therefore, here, we will investigate the role of neuronal and microglial TLR2 in tauopathy and wtTIDM peptide-mediated clearance of tauopathy and improvement in cognitive behaviors in P301S transgenic mice.