Department of Cellular Neurobiology, The Salk Institute for Biological Studies, La Jolla, California.
Department of Medicine, University of California San Diego, La Jolla.
J Gerontol A Biol Sci Med Sci. 2018 Mar 2;73(3):299-307. doi: 10.1093/gerona/glx104.
Alzheimer's disease (AD) is rarely addressed in the context of aging even though there is an overlap in pathology. We previously used a phenotypic screening platform based on old age-associated brain toxicities to identify the flavonol fisetin as a potential therapeutic for AD and other age-related neurodegenerative diseases. Based on earlier results with fisetin in transgenic AD mice, we hypothesized that fisetin would be effective against brain aging and cognitive dysfunction in rapidly aging senescence-accelerated prone 8 (SAMP8) mice, a model for sporadic AD and dementia. An integrative approach was used to correlate protein expression and metabolite levels in the brain with cognition. It was found that fisetin reduced cognitive deficits in old SAMP8 mice while restoring multiple markers associated with impaired synaptic function, stress, and inflammation. These results provide further evidence for the potential benefits of fisetin for the treatment of age-related neurodegenerative diseases.
阿尔茨海默病（AD）在衰老背景下很少被提及，尽管两者在病理学上存在重叠。我们之前使用了一种基于老年相关脑毒性的表型筛选平台，发现黄酮醇根皮素是 AD 和其他与年龄相关的神经退行性疾病的潜在治疗药物。基于根皮素在转基因 AD 小鼠中的早期研究结果，我们假设根皮素对快速衰老加速型 prone 8（SAMP8）小鼠的脑衰老和认知功能障碍有效，SAMP8 小鼠是散发性 AD 和痴呆的模型。采用综合方法将大脑中的蛋白质表达和代谢物水平与认知相关联。结果发现，根皮素可减少老年 SAMP8 小鼠的认知缺陷，同时恢复与突触功能障碍、应激和炎症相关的多个标志物。这些结果为根皮素治疗与年龄相关的神经退行性疾病的潜在益处提供了进一步的证据。
