ANG1-7 as an intervention for Alzheimer's Disease.

项目总结 本研究的目的是评价口服副乳杆菌对遗传的影响。 经修饰以表达血管紧张素(1-7)(Lp-A)治疗阿尔茨海默病(AD)。目标1将检验假设 病变初期的LP-A治疗将显著减缓或延缓PTAU和Aβ标记物的积聚 TgF344-AD大鼠的炎症、去甲肾上腺素能轴突丢失和海马突触功能障碍 依赖于mas受体的激活。目标2将检验LP-A治疗改善的假设 TgF344-AD大鼠在海马区依赖的行为测试中的表现和降低焦虑 依赖于mas受体的激活。预期影响：到目前为止，预防的有效治疗方法 缺乏年龄和AD介导的认知能力下降，因此对潜在有效干预的研究是 迫切需要。这项研究具有产生概念证明数据的巨大潜力，口头上- 只要干预改善或预防突触回路和认知功能的缺陷。这项工作是 意义重大，因为它解决了NIH认为关键的几个临床和公共卫生问题。 该项目的创新包括使用基因工程技术的概念方法来交付 益生菌形式的治疗化合物，以及为未来翻译奠定基础的研究设计 最终帮助人类解决阿尔茨海默病相关认知衰退带来的巨大健康负担。

PROJECT SUMMARY The objective of this study is to evaluate the impact of orally delivering Lactobacillus paracasei genetically modified to express Angiotensin (1-7) (LP-A) on Alzheimer’s Disease (AD). Aim 1 will test the hypothesis that LP-A treatment at the onset of pathology will significantly slow or delay accumulation of pTau and Aβ, markers of inflammation, loss of noradrenergic axons, and hippocampal synaptic dysfunction in TgF344-AD rats that is dependent upon activation of Mas receptors. Aim 2 will test the hypothesis that LP-A treatment improves performance in hippocampus-dependent behavioral assays and decreases anxiety in TgF344-AD rats that is dependent upon activation of Mas receptors. ANTICIPATED IMPACT: To date, proven treatments for preventing age- and AD mediated cognitive decline are lacking, thus research on potentially efficacious interventions is desperately needed. This study holds tremendous potential for generating proof of concept data that an orally- provided intervention improves or prevents deficits in synaptic circuit and cognitive function. The work is significant because it addresses several clinical and public health problems deemed critical by the NIH. Innovations in the project include the conceptual approach using genetic engineering techniques to deliver therapeutic compounds in probiotic form, and the study design which lays the groundwork for future translation to humans to ultimately help address the massive health burden of AD related cognitive decline.